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For: Kuniyasu H, Oue N, Wakikawa A, Shigeishi H, Matsutani N, Kuraoka K, Ito R, Yokozaki H, Yasui W. Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. J Pathol 2002;196:163-70. [PMID: 11793367 DOI: 10.1002/path.1031] [Citation(s) in RCA: 244] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

For:	Kuniyasu H, Oue N, Wakikawa A, Shigeishi H, Matsutani N, Kuraoka K, Ito R, Yokozaki H, Yasui W. Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. J Pathol 2002;196:163-70. [PMID: 11793367 DOI: 10.1002/path.1031] [Citation(s) in RCA: 244] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Number

Cited by Other Article(s)

Mori S, Fujiwara-Tani R, Ogata R, Ohmori H, Fujii K, Luo Y, Sasaki T, Nishiguchi Y, Bhawal UK, Kishi S, Kuniyasu H. Anti-Cancer and Pro-Immune Effects of Lauric Acid on Colorectal Cancer Cells. Int J Mol Sci 2025;26:1953. [PMID: 40076581 PMCID: PMC11901037 DOI: 10.3390/ijms26051953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 02/19/2025] [Accepted: 02/22/2025] [Indexed: 03/14/2025] Open

Affiliation(s)

Shiori Mori Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.) Department of Cancer Biology, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan
Rina Fujiwara-Tani Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Ruiko Ogata Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Hitoshi Ohmori Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Kiyomu Fujii Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Yi Luo Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Takamitsu Sasaki Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Yukiko Nishiguchi Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)
Ujjal Kumar Bhawal Research Institute of Oral Science, School of Dentistry at Matsudo, Nihon University, Matsudo 271-8587, Japan;
Shingo Kishi Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.) Department of Pathological Diagnosis, Nozaki Tokushukai Hospital, Daito 574-0074, Japan
Hiroki Kuniyasu Department of Molecular Pathology, School of Medicine, Nara Medical University, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (R.O.); (H.O.); (K.F.); (Y.L.); (T.S.); (Y.N.); (S.K.)

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Sloseris D, Forde NR. AGEing of collagen: The effects of glycation on collagen's stability, mechanics and assembly. Matrix Biol 2025;135:153-160. [PMID: 39805674 DOI: 10.1016/j.matbio.2024.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 12/12/2024] [Accepted: 12/13/2024] [Indexed: 01/16/2025]

Sasaki R, Luo Y, Kishi S, Ogata R, Nishiguchi Y, Sasaki T, Ohmori H, Fujiwara-Tani R, Kuniyasu H. Oxidative High Mobility Group Box-1 Accelerates Mitochondrial Transfer from Mesenchymal Stem Cells to Colorectal Cancer Cells Providing Cancer Cell Stemness. Int J Mol Sci 2025;26:1192. [PMID: 39940960 PMCID: PMC11818411 DOI: 10.3390/ijms26031192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open

Affiliation(s)

Rika Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Yi Luo Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.) Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan
Ruiko Ogata Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Yukiko Nishiguchi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (R.S.); (Y.L.); (S.K.); (R.O.); (Y.N.); (T.S.); (H.O.); (R.F.-T.)

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Fujiwara-Tani R, Luo Y, Ogata R, Fujii K, Sasaki T, Sasaki R, Nishiguchi Y, Mori S, Ohmori H, Kuniyasu H. Energy Metabolism and Stemness and the Role of Lauric Acid in Reversing 5-Fluorouracil Resistance in Colorectal Cancer Cells. Int J Mol Sci 2025;26:664. [PMID: 39859378 PMCID: PMC11766121 DOI: 10.3390/ijms26020664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/12/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open

Affiliation(s)

Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Yi Luo Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Ruiko Ogata Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Rika Sasaki Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Yukiko Nishiguchi Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Shiori Mori Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.) Department of Cancer Biology, Institute of Biomedical Science, Kansai Medical University, Osaka 573-1010, Japan
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University School of Medicine, Kashihara 634-8521, Japan; (Y.L.); (R.O.); (K.F.); (T.S.); (R.S.); (Y.N.); (S.M.); (H.O.)

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Fan J, Gillespie KP, Mesaros C, Blair IA. HMGB2-induced calreticulin translocation required for immunogenic cell death and ferroptosis of cancer cells are controlled by the nuclear exporter XPO1. Commun Biol 2024;7:1234. [PMID: 39354146 PMCID: PMC11445383 DOI: 10.1038/s42003-024-06930-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 09/20/2024] [Indexed: 10/03/2024] Open

Maier JA, Castiglioni S, Petrelli A, Cannatelli R, Ferretti F, Pellegrino G, Sarzi Puttini P, Fiorina P, Ardizzone S. Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison. Front Immunol 2024;15:1436581. [PMID: 39359726 PMCID: PMC11445042 DOI: 10.3389/fimmu.2024.1436581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/29/2024] [Indexed: 10/04/2024] Open

Zhang YY, Li YJ, Xue CD, Li S, Gao ZN, Qin KR. Effects of T2DM on cancer progression: pivotal precipitating factors and underlying mechanisms. Front Endocrinol (Lausanne) 2024;15:1396022. [PMID: 39290325 PMCID: PMC11405243 DOI: 10.3389/fendo.2024.1396022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 08/21/2024] [Indexed: 09/19/2024] Open

Liu M, Jiang H, Momeni MR. Epigenetic regulation of autophagy by non-coding RNAs and exosomal non-coding RNAs in colorectal cancer: A narrative review. Int J Biol Macromol 2024;273:132732. [PMID: 38823748 DOI: 10.1016/j.ijbiomac.2024.132732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/16/2024] [Accepted: 05/19/2024] [Indexed: 06/03/2024]

Luo Y, Fujiwara-Tani R, Kawahara I, Goto K, Nukaga S, Nishida R, Nakashima C, Sasaki T, Miyagawa Y, Ogata R, Fujii K, Ohmori H, Kuniyasu H. Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage. Int J Mol Sci 2024;25:7060. [PMID: 39000167 PMCID: PMC11241065 DOI: 10.3390/ijms25137060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/24/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open

Ryan AT, Kim M, Lim K. Immune Cell Migration to Cancer. Cells 2024;13:844. [PMID: 38786066 PMCID: PMC11120175 DOI: 10.3390/cells13100844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 04/27/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024] Open

Fujiwara-Tani R, Sasaki T, Bhawal UK, Mori S, Ogata R, Sasaki R, Ikemoto A, Kishi S, Fujii K, Ohmori H, Sho M, Kuniyasu H. Nuclear MAST4 Suppresses FOXO3 through Interaction with AKT3 and Induces Chemoresistance in Pancreatic Ductal Carcinoma. Int J Mol Sci 2024;25:4056. [PMID: 38612866 PMCID: PMC11012408 DOI: 10.3390/ijms25074056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/24/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open

Affiliation(s)

Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Ujjal Kumar Bhawal Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Matsudo 271-8587, Chiba, Japan;
Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Ruiko Ogata Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Rika Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Ayaka Ikemoto Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.) Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)
Masayuki Sho Department of Surgery, Nara Medical University, Kashihara 634-8522, Nara, Japan;
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (T.S.); (S.M.); (R.O.); (A.I.); (S.K.); (K.F.); (H.O.)

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Fujii K, Fujiwara-Tani R, Nukaga S, Ohmori H, Luo Y, Nishida R, Sasaki T, Miyagawa Y, Nakashima C, Kawahara I, Ogata R, Ikemoto A, Sasaki R, Kuniyasu H. Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene. Int J Mol Sci 2024;25:3015. [PMID: 38474261 DOI: 10.3390/ijms25053015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 02/25/2024] [Accepted: 03/02/2024] [Indexed: 03/14/2024] Open

Nishiguch Y, Fujiwara-Tani R, Nukaga S, Nishida R, Ikemoto A, Sasaki R, Mori S, Ogata R, Kishi S, Hojo Y, Shinohara H, Sho M, Kuniyasu H. Pterostilbene Induces Apoptosis from Endoplasmic Reticulum Stress Synergistically with Anticancer Drugs That Deposit Iron in Mitochondria. Int J Mol Sci 2024;25:2611. [PMID: 38473857 DOI: 10.3390/ijms25052611] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open

Gyoten M, Luo Y, Fujiwara-Tani R, Mori S, Ogata R, Kishi S, Kuniyasu H. Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria. Int J Mol Sci 2023;24:16814. [PMID: 38069135 PMCID: PMC10706654 DOI: 10.3390/ijms242316814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 11/24/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open

Liao WL, Lin H, Li YH, Yang TY, Chen MC. RAGE potentiates EGFR signaling and interferes with the anticancer effect of gefitinib on NSCLC cells. Am J Physiol Cell Physiol 2023;325:C1313-C1325. [PMID: 37746694 DOI: 10.1152/ajpcell.00494.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 09/18/2023] [Accepted: 09/18/2023] [Indexed: 09/26/2023]

Abstract

The receptor for advanced glycation end-products (RAGE) has been implicated in tumorigenesis, whereas epidermal growth factor receptor (EGFR) signaling plays a vital role in lung cancer progression. Both RAGE and EGFR are transmembrane receptors that transmit intracellular signals through ligand binding, and their downstream signaling cascades show substantial overlap. However, the interplay between these two molecules remains poorly understood. In the present study, we evaluated the correlation between RAGE and EGFR in the tumorigenesis of non-small cell lung cancer (NSCLC) and evaluated the impact of RAGE on the response of NSCLC cells to gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). The expression and activation of EGFR and the phosphorylation of its downstream molecules, signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (Erk), were increased in RAGE-overexpressed A549 (A549-RAGE) cells. Notably, ligand-triggered activation of EGFR signaling was significantly greater in A549-RAGE compared with A549-parental cells. In addition, gefitinib had less effect on the inhibition of EGFR signaling in A549-RAGE cells. These findings were validated in other NSCLC cell lines, H1299 and H1975. Furthermore, upon gefitinib administration, the antiapoptotic marker B-cell lymphoma 2 (Bcl-2) expression was upregulated in A549-RAGE cells, whereas the apoptotic markers Bcl-2 associated X protein (Bax) and Bcl-2 interacting mediator (Bim) remained at lower levels compared with A549-parental cells. Importantly, our findings provide evidence that RAGE interferes with the anticancer effect of gefitinib by modulating the activation of EGFR-STAT3 and EGFR-Erk pathways. Overall, these significant findings deepen our understanding of the intricate relationship between RAGE and EGFR signaling in NSCLC tumorigenesis and provide new considerations for the clinical treatment of NSCLC.NEW & NOTEWORTHY This study represents a pioneering endeavor in comprehending the intricate interplay between RAGE and EGFR signaling within NSCLC. The findings reveal that RAGE serves to enhance EGFR phosphorylation and activation, consequently modulating apoptosis regulators through the EGFR-STAT3 and EGFR-Erk1/2 signaling pathways. Through this mechanism, RAGE potentially imparts resistance to the toxicity induced by EGFR-TKIs in NSCLC cells.

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Chang TY, Lan KC, Wu CH, Sheu ML, Yang RS, Liu SH. Nε-(1-Carboxymethyl)-L-lysine, an advanced glycation end product, exerts malignancy on chondrosarcoma via the activation of cancer stemness. Arch Toxicol 2023;97:2231-2244. [PMID: 37314482 DOI: 10.1007/s00204-023-03539-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 06/06/2023] [Indexed: 06/15/2023]

DU K, Wu X, Ji X, Liang N, Li Z. Early growth response 1 promoted the invasion of glioblastoma multiforme by elevating HMGB1. J Neurosurg Sci 2023;67:422-430. [PMID: 33297605 DOI: 10.23736/s0390-5616.20.05107-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]

Magna M, Hwang GH, McIntosh A, Drews-Elger K, Takabatake M, Ikeda A, Mera BJ, Kwak T, Miller P, Lippman ME, Hudson BI. RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer. NPJ Breast Cancer 2023;9:59. [PMID: 37443146 DOI: 10.1038/s41523-023-00564-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic cancer subtype, which is generally untreatable once it metastasizes. We hypothesized that interfering with the Receptor for Advanced Glycation End-products (RAGE) signaling with the small molecule RAGE inhibitors (TTP488/Azeliragon and FPS-ZM1) would impair TNBC metastasis and impair fundamental mechanisms underlying tumor progression and metastasis. Both TTP488 and FPS-ZM1 impaired spontaneous and experimental metastasis of TNBC models, with TTP488 reducing metastasis to a greater degree than FPS-ZM1. Transcriptomic analysis of primary xenograft tumor and metastatic tissue revealed high concordance in gene and protein changes with both drugs, with TTP488 showing greater potency against metastatic driver pathways. Phenotypic validation of transcriptomic analysis by functional cell assays revealed that RAGE inhibition impaired TNBC cell adhesion to multiple extracellular matrix proteins (including collagens, laminins, and fibronectin), migration, and invasion. Neither RAGE inhibitor impaired cellular viability, proliferation, or cell cycle in vitro. Proteomic analysis of serum from tumor-bearing mice revealed RAGE inhibition affected metastatic driver mechanisms, including multiple cytokines and growth factors. Further mechanistic studies by phospho-proteomic analysis of tumors revealed RAGE inhibition led to decreased signaling through critical BC metastatic driver mechanisms, including Pyk2, STAT3, and Akt. These results show that TTP488 impairs metastasis of TNBC and further clarifies the signaling and cellular mechanisms through which RAGE mediates metastasis. Importantly, as TTP488 displays a favorable safety profile in human studies, our study provides the rationale for evaluating TTP488 in clinical trials to treat or prevent metastatic TNBC.

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Affiliation(s)

Melinda Magna Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, USA Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Gyong Ha Hwang Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, USA
Alec McIntosh Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Katherine Drews-Elger Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Masaru Takabatake Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Adam Ikeda Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Barbara J Mera Department of Cell Biology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
Taekyoung Kwak Department of Cell Biology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
Philip Miller Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Marc E Lippman Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA
Barry I Hudson Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, USA. Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Washington, DC, USA. Department of Cell Biology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.

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Dorf J, Pryczynicz A, Matowicka-Karna J, Zaręba K, Żukowski P, Zalewska A, Maciejczyk M. Could circulating biomarkers of nitrosative stress and protein glycoxidation be useful in patients with gastric cancer? Front Oncol 2023;13:1213802. [PMID: 37503318 PMCID: PMC10369187 DOI: 10.3389/fonc.2023.1213802] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 06/23/2023] [Indexed: 07/29/2023] Open

Abstract

Background

Nitrosative stress leads to protein glycoxidation, but both processes may be strongly related to the cancer development. Therefore, the aim of this study was to assess the nitrosative stress and protein glycoxidation products in patients with gastric cancer in comparison with healthy controls. We are also the first to evaluate the diagnostic utility of nitrosative stress and protein glycoxidation markers in gastric cancer patients in respect to histopathological classifications (TNM, Lauren's and Goseki's classification) and histopathological parameters such as histological type, histological differentiation grade, presence of vascular or neural invasion, desmoplasia and Helicobacter pylori infection.

Methods

The study included 50 patients with gastric cancer and 50 healthy controls matched for sex and age. Nitrosative stress parameters and protein glycoxidation products were measured colorimetrically/fluorometrically in plasma or serum samples. Student's t-test or Mann-Whitney U-test were used for statistical analysis.

Results

NO, S-nitrosothiols, nitrotyrosine, kynurenine, N-formylkynurenine, dityrosine, AGE and Amadori products were significantly increased whereas tryptophan fluorescence was decreased in patients with gastric cancer compared to the healthy control. Nitrosative stress and glycoxidation products may be useful in diagnosis of gastric cancer because they differentiate patients with gastric cancer from healthy individuals with high sensitivity and specificity. Some of the determined parameters are characterised by high AUC value in differentiation of GC patients according to the histopathological parameters.

Conclusions

Gastric cancer is associated with enhanced circulating nitrosative stress and protein glycation. Although further research on a tissue model is needed, plasma/serum biomarkers may be dependent on tumour size, histological type, tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion and Helicobacter pylori infection. Thus, circulating biomarkers of nitrosative stress/protein glycoxidation may have potential diagnostic significance in gastric cancer patients.

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Dai X, Hou Y, Deng T, Lin G, Cao Y, Yu G, Wei W, Zheng Q, Huang L, Ma S. A specific RAGE-binding peptide inhibits triple negative breast cancer growth through blocking of Erk1/2/NF-κB pathway. Eur J Pharmacol 2023;954:175861. [PMID: 37380046 DOI: 10.1016/j.ejphar.2023.175861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 06/12/2023] [Accepted: 06/15/2023] [Indexed: 06/30/2023]

Affiliation(s)

Xiaoyong Dai Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China
Yibo Hou Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China
Ting Deng Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China
Gaoyang Lin Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China
Yuanxiong Cao Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China
Guiyuan Yu Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University, Shenzhen, Guangdong, China
Wei Wei The Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China
Qing Zheng College of Pharmacy, Jinan University, 510632 Guangzhou, Guangdong, People's Republic of China
Laiqiang Huang Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China.
Shaohua Ma Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, 518055, China.

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Mori S, Fujiwara-Tani R, Gyoten M, Nukaga S, Sasaki R, Ikemoto A, Ogata R, Kishi S, Fujii K, Kuniyasu H. Berberine Induces Combined Cell Death in Gastrointestinal Cell Lines. Int J Mol Sci 2023;24:ijms24076588. [PMID: 37047563 PMCID: PMC10094831 DOI: 10.3390/ijms24076588] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/21/2023] [Accepted: 03/29/2023] [Indexed: 04/05/2023] Open

Chen MC, Yang BZ, Kuo WW, Wu SH, Wang TF, Yeh YL, Chen MC, Huang CY. The involvement of Aurora-A and p53 in oxaliplatin-resistant colon cancer cells. J Cell Biochem 2023;124:619-632. [PMID: 36976911 DOI: 10.1002/jcb.30394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/11/2022] [Accepted: 02/24/2023] [Indexed: 03/30/2023]

Rojas A, Lindner C, Schneider I, González I, Morales MA. Contributions of the receptor for advanced glycation end products axis activation in gastric cancer. World J Gastroenterol 2023;29:997-1010. [PMID: 36844144 PMCID: PMC9950863 DOI: 10.3748/wjg.v29.i6.997] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/26/2022] [Accepted: 01/11/2023] [Indexed: 02/10/2023] Open

Faruqui T, Singh G, Khan S, Khan MS, Akhter Y. Differential gene expression analysis of RAGE-S100A6 complex for target selection and the design of novel inhibitors for anticancer drug discovery. J Cell Biochem 2023;124:205-220. [PMID: 36502516 DOI: 10.1002/jcb.30356] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/15/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022]

Sugary drink consumption and the subsequent risk of gastric cancer: The Japan Public Health Center-based Prospective Study. Eur J Clin Nutr 2023;77:218-225. [PMID: 36167978 DOI: 10.1038/s41430-022-01216-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 11/08/2022]

RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review. Int J Mol Sci 2022;24:ijms24010266. [PMID: 36613714 PMCID: PMC9820344 DOI: 10.3390/ijms24010266] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 10/28/2022] [Accepted: 12/16/2022] [Indexed: 12/28/2022] Open

Shkrigunov T, Kisrieva Y, Samenkova N, Larina O, Zgoda V, Rusanov A, Romashin D, Luzgina N, Karuzina I, Lisitsa A, Petushkova N. Comparative proteoinformatics revealed the essentials of SDS impact on HaCaT keratinocytes. Sci Rep 2022;12:21437. [PMID: 36509991 PMCID: PMC9744838 DOI: 10.1038/s41598-022-25934-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open

An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma. Int J Mol Sci 2022;23:ijms231810704. [PMID: 36142607 PMCID: PMC9506332 DOI: 10.3390/ijms231810704] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 12/03/2022] Open

Abstract Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human oral squamous cell carcinoma (OSCC) are unclear. In this study, we investigated HOXA11-AS expression and function in human OSCC tissues and cell lines, as well as a mouse model of OSCC. Our analyses showed that HOXA11-AS expression in human OSCC cases correlates with lymph node metastasis, nicotinamide adenine dinucleotide (NAD)(P)H: quinone oxidoreductase 1 (NQO1) upregulation, and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) downregulation. Using the human OSCC cell lines HSC3 and HSC4, we demonstrate that HOXA11-AS promotes NQO1 expression by sponging microRNA-494. In contrast, HOXA11-AS recruits zeste homolog 2 (EZH2) to the NQO2 promoter to suppress its expression via the trimethylation of H3K27. The upregulation of NQO1 enzymatic activity by HOXA11-AS results in the consumption of flavin adenine dinucleotide (FAD), which reduces FAD-requiring glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and suppresses glycolysis. However, our analyses show that lactic acid fermentation levels are preserved by glutaminolysis due to increased malic enzyme-1 expression, promoting enhanced proliferation, invasion, survival, and drug resistance. In contrast, suppression of NQO2 expression reduces the consumption of NRH via NQO2 enzymatic activity and increases NAD levels, which promotes enhanced stemness and metastatic potential. In mouse tumor models, knockdown of HOXA11-AS markedly suppressed tumor growth and lung metastasis. From these findings, targeting HOXA11-AS may strongly suppress high-grade OSCC by regulating both NQO1 and NQO2. Collapse

Fujiwara-Tani R, Sasaki T, Takagi T, Mori S, Kishi S, Nishiguchi Y, Ohmori H, Fujii K, Kuniyasu H. Gemcitabine Resistance in Pancreatic Ductal Carcinoma Cell Lines Stems from Reprogramming of Energy Metabolism. Int J Mol Sci 2022;23:ijms23147824. [PMID: 35887170 PMCID: PMC9323155 DOI: 10.3390/ijms23147824] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 02/05/2023] Open

Li L, Beeraka NM, Xie L, Dong L, Liu J, Wang L. Co-expression of High-mobility group box 1 protein (HMGB1) and receptor for advanced glycation end products (RAGE) in the prognosis of esophageal squamous cell carcinoma. Discov Oncol 2022;13:64. [PMID: 35829833 PMCID: PMC9279518 DOI: 10.1007/s12672-022-00527-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 06/15/2022] [Indexed: 12/24/2022] Open

Maesaka F, Kuwada M, Horii S, Kishi S, Fujiwara-Tani R, Mori S, Fujii K, Mori T, Ohmori H, Owari T, Miyake M, Nakai Y, Tanaka N, Bhawal UK, Luo Y, Kondoh M, Fujimoto K, Kuniyasu H. Hypomethylation of CLDN4 Gene Promoter Is Associated with Malignant Phenotype in Urinary Bladder Cancer. Int J Mol Sci 2022;23:ijms23126516. [PMID: 35742959 PMCID: PMC9224287 DOI: 10.3390/ijms23126516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 06/03/2022] [Accepted: 06/08/2022] [Indexed: 12/04/2022] Open

Affiliation(s)

Fumisato Maesaka Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.) Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Masaomi Kuwada Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.) Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Shohei Horii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Takuya Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.)
Takuya Owari Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Makito Miyake Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Yasushi Nakai Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Nobumichi Tanaka Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Ujjal Kumar Bhawal Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.) Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India
Yi Luo Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China;
Masuo Kondoh Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University, 6-1 Yamadaoka, Suita 565-0871, Osaka, Japan;
Kiyohide Fujimoto Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan; (T.O.); (M.M.); (Y.N.); (N.T.); (K.F.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; (F.M.); (M.K.); (S.H.); (S.K.); (R.F.-T.); (S.M.); (K.F.); (T.M.); (H.O.); (U.K.B.) Correspondence: ; Tel.: +81-744-22-3051; Fax: +81-744-25-7308

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Kishi S, Fujiwara-Tani R, Honoki K, Sasaki R, Mori S, Ohmori H, Sasaki T, Miyagawa Y, Kawahara I, Kido A, Tanaka Y, Kuniyasu H. Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells. Cancer Sci 2022;113:2904-2915. [PMID: 35570394 PMCID: PMC9357642 DOI: 10.1111/cas.15400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 11/26/2022] Open

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8. Int J Mol Sci 2022;23:ijms23074002. [PMID: 35409367 PMCID: PMC8999764 DOI: 10.3390/ijms23074002] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/30/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023] Open

Mechanism of Herb Pairs Astragalus mongholicus and Curcuma phaeocaulis Valeton in Treating Gastric Carcinoma: A Network Pharmacology Combines with Differential Analysis and Molecular Docking. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022;2022:8361431. [PMID: 35321506 PMCID: PMC8938068 DOI: 10.1155/2022/8361431] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/07/2022] [Accepted: 02/11/2022] [Indexed: 02/08/2023]

Abstract

Background

Gastric carcinoma (GC) is a kind of digestive tract tumor that is highly malignant and has a very poor prognosis. Although both Astragalus mongholicus (AM, huáng qí) and Curcuma phaeocaulis Valeton (CPV, é zhú) can slow the onset and progression of GC, the mechanism by which AM-CPV works in the treatment of GC is uncertain.

Materials and Methods

The traditional Chinese medicine network databases TCMSP, TCMID, and ETCM were used to identify the key functional components and associated targets of AM and CPV. To establish a theoretical foundation, the development of gastric cancer (GC) was predicted utilizing a GEO gene chip and TCGA difference analysis mixed with network pharmacology. A herbal-ingredient-target network and a core target-signal pathway network were created using GO and KEGG enrichment analyses. The molecular docking method was used to evaluate seventeen main targets and their compounds.

Results

Cell activity, reactive oxygen species modification, metabolic regulation, and systemic immune activation may all be involved in the action mechanism of the AM-CPV drug-pair in the treatment of GC. It inhibits the calcium signaling route, the AGE-RAGE signaling system, the cAMP signaling pathway, the PI3K-Akt signaling network, and the MAPK signaling pathway, slowing the progression of GC. The number of inflammatory substances in the tumor microenvironment is reduced, GC cell proliferation is deprived, apoptosis is promoted, and GC progression is retarded through controlling the IL-17 signaling route, TNF signaling pathway, and other inflammation-related pathways.

Conclusions

The AM-CPV pharmaceutical combination regulates GC treatment via a multitarget, component, and signal pathway with a cooperative and bidirectional regulatory mechanism. Its active constituents may treat GC by regulating the expression of STAT1, MMP9, IL6, HSP90AA1, JUN, CCL2, IFNG, CXCL8, and other targets, as well as activating or inhibiting immune-inflammatory and cancer signaling pathways.

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Zhu B, Qu S. The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms. Front Endocrinol (Lausanne) 2022;13:800995. [PMID: 35222270 PMCID: PMC8873103 DOI: 10.3389/fendo.2022.800995] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 01/12/2022] [Indexed: 12/27/2022] Open

Shipunov I, Kupaev V. Glycome assessment in patients with respiratory diseases. TRANSLATIONAL METABOLIC SYNDROME RESEARCH 2022. [DOI: 10.1016/j.tmsr.2022.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2022] Open

Impact of Advanced Glycation End products (AGEs) and its receptor (RAGE) on cancer metabolic signaling pathways and its progression. Glycoconj J 2022;38:717-734. [PMID: 35064413 DOI: 10.1007/s10719-021-10031-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023]

Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma. Angiogenesis 2021;25:181-203. [PMID: 34617194 PMCID: PMC8494172 DOI: 10.1007/s10456-021-09819-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 08/04/2021] [Indexed: 01/15/2023]

Abstract

Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). High densities of peritumoral proliferating B cells and concomitantly high intratumoral HMGB1 expression showed improved prognostic significance, surpassing prognostic stratification of ESCC patients based on HMGB1 positivity alone. This striking association led us to set up models to test whether cancer-derived HMGB1 could shape tumor microenvironment via modulation on B cells. Overexpression of HMGB1 in ESCC cell lines (KYSE510 and EC18) enhanced proliferation and migration of B cells. Transcriptomic analysis showed that migratory B cells exhibited high enrichment of proangiogenic genes. VEGF expression in proliferating B cells was induced upon co-culture of HMGB1-overexpressing tumor cells and B cells. Secretome array profiling of conditioned media (CM) from the co-culture revealed rich expression of proangiogenic proteins. Consequently, incubation of human umbilical vein endothelial cells with CM promoted angiogenesis in tube formation and migration assays. HMGB1 inhibitor, glycyrrhizin, abolishes all the observed proangiogenic phenotypes. Finally, co-injection of B cells and CM with HMGB1-overexpressing tumor cells, but not with glycyrrhizin, significantly enhanced tumor growth associated with increased microvascular density in ESCC xenograft mice model. Our results indicate that cancer-derived HMGB1 elevates angiogenesis in ESCC by shifting the balance toward proangiogenic signals in proliferating B cells.

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Mori S, Fujiwara-Tani R, Kishi S, Sasaki T, Ohmori H, Goto K, Nakashima C, Nishiguchi Y, Kawahara I, Luo Y, Kuniyasu H. Enhancement of Anti-Tumoral Immunity by β-Casomorphin-7 Inhibits Cancer Development and Metastasis of Colorectal Cancer. Int J Mol Sci 2021;22:ijms22158232. [PMID: 34360996 PMCID: PMC8348766 DOI: 10.3390/ijms22158232] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/14/2021] [Accepted: 07/28/2021] [Indexed: 01/24/2023] Open

Affiliation(s)

Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Kei Goto Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Chie Nakashima Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Yukiko Nishiguchi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Isao Kawahara Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.)
Yi Luo Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China Correspondence: (Y.L.); (H.K.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan; (S.M.); (R.F.-T.); (S.K.); (T.S.); (H.O.); (K.G.); (C.N.); (Y.N.); (I.K.) Correspondence: (Y.L.); (H.K.)

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Hypoxia and the Receptor for Advanced Glycation End Products (RAGE) Signaling in Cancer. Int J Mol Sci 2021;22:ijms22158153. [PMID: 34360919 PMCID: PMC8348933 DOI: 10.3390/ijms22158153] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/25/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open

Marulanda K, Mercel A, Gillis DC, Sun K, Gambarian M, Roark J, Weiss J, Tsihlis ND, Karver MR, Centeno SR, Peters EB, Clemons TD, Stupp SI, McLean SE, Kibbe MR. Intravenous Delivery of Lung-Targeted Nanofibers for Pulmonary Hypertension in Mice. Adv Healthc Mater 2021;10:e2100302. [PMID: 34061473 PMCID: PMC8273153 DOI: 10.1002/adhm.202100302] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/15/2021] [Indexed: 01/11/2023]

Affiliation(s)

Kathleen Marulanda Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Alexandra Mercel Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
David C Gillis Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Kui Sun Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Maria Gambarian Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Joshua Roark Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Jenna Weiss Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Nick D Tsihlis Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Mark R Karver Simpson Querrey Institute, Northwestern University, 303 E. Superior Street, Chicago, IL, 60611, USA
S Ruben Centeno Department of Pediatrics, University of North Carolina, 260 MacNider Building CB# 7220, Chapel Hill, NC, 27599, USA
Erica B Peters Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Tristan D Clemons Simpson Querrey Institute, Northwestern University, 303 E. Superior Street, Chicago, IL, 60611, USA
Samuel I Stupp Simpson Querrey Institute, Northwestern University, 303 E. Superior Street, Chicago, IL, 60611, USA
Sean E McLean Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA
Melina R Kibbe Department of Surgery, University of North Carolina, 4041 Burnett Womack, 101 Manning Drive, Chapel Hill, NC, 27599, USA

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Kishi S, Nishiguchi Y, Honoki K, Mori S, Fujiwara-Tani R, Sasaki T, Fujii K, Kawahara I, Goto K, Nakashima C, Kido A, Tanaka Y, Luo Y, Kuniyasu H. Role of Glycated High Mobility Group Box-1 in Gastric Cancer. Int J Mol Sci 2021;22:5185. [PMID: 34068442 PMCID: PMC8153607 DOI: 10.3390/ijms22105185] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/06/2021] [Accepted: 05/11/2021] [Indexed: 12/30/2022] Open

Abstract

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. Nε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.

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Affiliation(s)

Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Yukiko Nishiguchi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Kanya Honoki Department of Orthopedics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (K.H.); (A.K.); (Y.T.)
Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Isao Kawahara Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Kei Goto Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Chie Nakashima Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)
Akira Kido Department of Orthopedics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (K.H.); (A.K.); (Y.T.)
Yasuhito Tanaka Department of Orthopedics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (K.H.); (A.K.); (Y.T.)
Yi Luo Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.) Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (S.K.); (Y.N.); (S.M.); (R.F.-T.); (T.S.); (K.F.); (I.K.); (K.G.); (C.N.)

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Chilelli NC, Faggian A, Favaretto F, Milan G, Compagnin C, Dassie F, Bettini S, Roverso M, Seraglia R, Lapolla A, Vettor R. In vitro chronic glycation induces AGEs accumulation reducing insulin-stimulated glucose uptake and increasing GLP1R in adipocytes. Am J Physiol Endocrinol Metab 2021;320:E976-E988. [PMID: 33779307 DOI: 10.1152/ajpendo.00156.2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]

Banerjee S. Long-term incubation of myoglobin with glyoxal induces amyloid like aggregation of the heme protein: Implications of advanced glycation end products in protein conformational disorders. J Mol Liq 2021. [DOI: 10.1016/j.molliq.2020.115256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]

Mukherjee TK, Malik P, Hoidal JR. Receptor for Advanced Glycation End Products (RAGE) and Its Polymorphic Variants as Predictive Diagnostic and Prognostic Markers of NSCLCs: a Perspective. Curr Oncol Rep 2021;23:12. [PMID: 33399986 DOI: 10.1007/s11912-020-00992-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/05/2020] [Indexed: 12/24/2022]

Anti-Stem Cell Property of Pterostilbene in Gastrointestinal Cancer Cells. Int J Mol Sci 2020;21:ijms21249347. [PMID: 33302440 PMCID: PMC7762551 DOI: 10.3390/ijms21249347] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 12/06/2020] [Indexed: 12/17/2022] Open

Owari T, Sasaki T, Fujii K, Fujiwara-Tani R, Kishi S, Mori S, Mori T, Goto K, Kawahara I, Nakai Y, Miyake M, Luo Y, Tanaka N, Kondoh M, Fujimoto K, Kuniyasu H. Role of Nuclear Claudin-4 in Renal Cell Carcinoma. Int J Mol Sci 2020;21:ijms21218340. [PMID: 33172177 PMCID: PMC7664319 DOI: 10.3390/ijms21218340] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 10/28/2020] [Accepted: 11/04/2020] [Indexed: 12/22/2022] Open

Abstract

Claudin-4 (CLDN4) is a tight junction protein to maintain the cancer microenvironment. We recently reported the role of the CLDN4 not forming tight junction in the induction of epithelial-mesenchymal transition (EMT). Herein, we investigated the role of CLDN4 in renal cell carcinoma (RCC), focusing on CLDN4. CLDN4 expression in 202 RCCs was examined by immunostaining. CLDN4 phosphorylation and subcellular localization were examined using high metastatic human RCC SN12L1 and low metastatic SN12C cell lines. In 202 RCC cases, the CLDN4 expression decreased in the cell membrane and had no correlation with clinicopathological factors. However, CLDN4 was localized in the nucleus in 5 cases (2%), all of which were pT3. Contrastingly, only 6 of 198 nuclear CLDN4-negative cases were pT3. CLDN4 was found in the nuclear fraction of a highly metastatic human RCC cell line, SN12L1, but not in the low metastatic SN12C cells. In SN12L1 cells, phosphorylation of tyrosine and serine residues was observed in cytoplasmic CLDN4, but not in membranous CLDN4. In contrast, phosphorylation of serine residues was observed in nuclear CLDN4. In SN12L1 cells, CLDN4 tyrosine phosphorylation by EphA2/Ephrin A1 resulted in the release of CLDN4 from tight junction and cytoplasmic translocation. Furthermore, protein kinase C (PKC)-ε phosphorylated the CLDN4 serine residue, resulting in nuclear import. Contrarily, in SN12C cells that showed decreased expression of EphA2/Ephrin A1 and PKCε, the activation of EphA2/EphrinA1 and PKCε induced cytoplasmic and nuclear translocation of CLDN4, respectively. Furthermore, the nuclear translocation of CLDN4 promoted the nuclear translocation of Yes-associated protein (YAP) bound to CLDN4, which induced the EMT phenotype. These findings suggest that the release of CLDN4 by impaired tight junction might be a mechanism underlying the malignant properties of RCC. These findings suggest that the release of CLDN4 by impaired tight junction might be one of the mechanisms of malignant properties of RCC.

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Affiliation(s)

Takuya Owari Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.) Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (Y.N.); (M.M.); (N.T.)
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Takuya Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Kei Goto Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Isao Kawahara Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.)
Yasushi Nakai Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (Y.N.); (M.M.); (N.T.)
Makito Miyake Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (Y.N.); (M.M.); (N.T.)
Yi Luo Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.) Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China
Nobumichi Tanaka Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (Y.N.); (M.M.); (N.T.)
Masuo Kondoh Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University, 6-1 Yamadaoka, Suita, Osaka 565-0871, Japan;
Kiyohide Fujimoto Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (Y.N.); (M.M.); (N.T.) Correspondence: (K.F.); (H.K.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (T.O.); (T.S.); (K.F.); (R.F.-T.); (S.K.); (S.M.); (T.M.); (K.G.); (I.K.); (Y.L.) Correspondence: (K.F.); (H.K.)

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Swami P, Thiyagarajan S, Vidger A, Indurthi VSK, Vetter SW, Leclerc E. RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells. Int J Mol Sci 2020;21:E7723. [PMID: 33086527 PMCID: PMC7589276 DOI: 10.3390/ijms21207723] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/15/2020] [Accepted: 10/15/2020] [Indexed: 12/16/2022] Open

Miyagawa Y, Nukaga S, Mori T, Fujiwara-Tani R, Fujii K, Mori S, Goto K, Kishi S, Sasaki T, Nakashima C, Ohmori H, Kawahara I, Luo Y, Kuniyasu H. Evaluation of cancer-derived myocardial impairments using a mouse model. Oncotarget 2020;11:3712-3722. [PMID: 33110478 PMCID: PMC7566807 DOI: 10.18632/oncotarget.27759] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 09/10/2020] [Indexed: 01/21/2023] Open

Nakashima C, Kirita T, Yamamoto K, Mori S, Luo Y, Sasaki T, Fujii K, Ohmori H, Kawahara I, Mori T, Goto K, Kishi S, Fujiwara-Tani R, Kuniyasu H. Malic Enzyme 1 Is Associated with Tumor Budding in Oral Squamous Cell Carcinomas. Int J Mol Sci 2020;21:ijms21197149. [PMID: 32998265 PMCID: PMC7582746 DOI: 10.3390/ijms21197149] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/23/2020] [Accepted: 09/24/2020] [Indexed: 12/14/2022] Open

Abstract

Budding at the tumor invasive front has been correlated with the malignant properties of many cancers. Malic enzyme 1 (ME1) promotes the Warburg effect in cancer cells and induces epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Therefore, we investigated the role of ME1 in tumor budding in OSCC. Tumor budding was measured in 96 human OSCCs by immunostaining for an epithelial marker (AE1/AE3), and its expression was compared with that of ME1. A significant correlation was observed between tumor budding and ME1 expression. The correlation increased with the progression of cancer. In human OSCC cells, lactate secretion decreased when lactate fermentation was suppressed by knockdown of ME1 and lactate dehydrogenase A or inhibition of pyruvate dehydrogenase (PDH) kinase. Furthermore, the extracellular pH increased, and the EMT phenotype was suppressed. In contrast, when oxidative phosphorylation was suppressed by PDH knockdown, lactate secretion increased, extracellular pH decreased, and the EMT phenotype was promoted. Induction of chemical hypoxia in OSCC cells by CoCl₂ treatment resulted in increased ME1 expression along with HIF1α expression and promotion of the EMT phenotype. Hypoxic conditions also increased matrix metalloproteinases expression and decreased mitochondrial membrane potential, mitochondrial oxidative stress, and extracellular pH. Furthermore, the hypoxic treatment resulted in the activation of Yes-associated protein (YAP), which was abolished by ME1 knockdown. These findings suggest that cancer cells at the tumor front in hypoxic environments increase their lactate secretion by switching their energy metabolism from oxidative phosphorylation to glycolysis owing to ME1 overexpression, decrease in extracellular pH, and YAP activation. These alterations enhance EMT and the subsequent tumor budding. Tumor budding and ME1 expression are thus considered useful markers of OSCC malignancy, and ME1 is expected to be a relevant target for molecular therapy.

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Affiliation(s)

Chie Nakashima Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.) Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan;
Tadaaki Kirita Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; Correspondence: (T.K.); (H.K.); Tel.: +81-744-22-3051 (T.K. & H.K.); Fax: +81-744-25-7308 (H.K.)
Kazuhiko Yamamoto Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan;
Shiori Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Yi Luo Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China;
Takamitsu Sasaki Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Kiyomu Fujii Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Hitoshi Ohmori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Isao Kawahara Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Takuya Mori Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Kei Goto Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Shingo Kishi Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Rina Fujiwara-Tani Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.)
Hiroki Kuniyasu Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (C.N.); (S.M.); (T.S.); (K.F.); (H.O.); (I.K.); (T.M.); (K.G.); (S.K.); (R.F.-T.) Correspondence: (T.K.); (H.K.); Tel.: +81-744-22-3051 (T.K. & H.K.); Fax: +81-744-25-7308 (H.K.)

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