Meng M, Chen Q, Yuan M, Guo X, Ren SQ, Yuan CH. T-LAK cell-originated protein kinase promotes tumorigenesis and metastasis of pancreatic neuroendocrine neoplasms via mitogen-activated protein kinase axis activation. World J Gastrointest Surg 2026; 18(4): 115798 [DOI: 10.4240/wjgs.v18.i4.115798]
Corresponding Author of This Article
Chun-Hui Yuan, MD, Department of General Surgery, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, China. ychdoctor@bjmu.edu.cn
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Oncology
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Basic Study
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Apr 27, 2026 (publication date) through Apr 24, 2026
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Publication Name
World Journal of Gastrointestinal Surgery
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1948-9366
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Meng M, Chen Q, Yuan M, Guo X, Ren SQ, Yuan CH. T-LAK cell-originated protein kinase promotes tumorigenesis and metastasis of pancreatic neuroendocrine neoplasms via mitogen-activated protein kinase axis activation. World J Gastrointest Surg 2026; 18(4): 115798 [DOI: 10.4240/wjgs.v18.i4.115798]
World J Gastrointest Surg. Apr 27, 2026; 18(4): 115798 Published online Apr 27, 2026. doi: 10.4240/wjgs.v18.i4.115798
T-LAK cell-originated protein kinase promotes tumorigenesis and metastasis of pancreatic neuroendocrine neoplasms via mitogen-activated protein kinase axis activation
Meng Meng, Qing Chen, Meng Yuan, Si-Qian Ren, Chun-Hui Yuan, Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
Xin Guo, Department of Medicine, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
Co-first authors: Meng Meng and Qing Chen.
Author contributions: Meng M and Chen Q performed experiments, prepared the manuscript, contributed equally to this manuscript and are co-first authors; Meng M, Chen Q, Yuan M, Guo X, Ren SQ, and Yuan CH reviewed experimental progression, interpreted experimental data, reviewed and edited manuscripts; Meng M, Chen Q, and Yuan CH designed and oversaw experiments. All authors reviewed and approved the final version.
Supported by National Natural Science Foundation of China, No. 81672862; and the National Science and Technology Major Project of China, No. 2025ZD0552411.
Institutional review board statement: This study was approved by the Ethic Committee of Peking University Third Hospital (Approval No. IRB00006761-2016128).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data in this study are available from the corresponding author upon request.
Corresponding author: Chun-Hui Yuan, MD, Department of General Surgery, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing 100191, China. ychdoctor@bjmu.edu.cn
Received: November 21, 2025 Revised: December 19, 2025 Accepted: February 9, 2026 Published online: April 27, 2026 Processing time: 153 Days and 22.1 Hours
Abstract
BACKGROUND
In pancreatic neuroendocrine neoplasms (pNENs) with liver metastasis, marked upregulation of T-LAK cell-originated protein kinase (TOPK) is associated with poor prognosis.
AIM
To elucidate the role of TOPK in pNEN progression and metastasis and to explore the underlying mechanisms. The therapeutic potential of the TOPK inhibitor HI-TOPK-032 was further investigated to inform targeted treatment strategies.
METHODS
TOPK expression was assessed in tissue samples from 23 patients with pNENs, with and without liver metastasis. TOPK was knocked down in the BON-1 cell line to examine its effects on cell proliferation, epithelial-mesenchymal transition, and activation of the mitogen-activated protein kinase (MAPK) axis. RNA-seq analyzed gene expression changes following TOPK knockdown. The effects of HI-TOPK-032 on pNENs cell proliferation, migration, and invasiveness were also evaluated.
RESULTS
TOPK was significantly upregulated in pNENs with liver metastasis and correlated with poorer overall survival. TOPK knockdown in BON-1 cells reduced proliferative capacity and epithelial-mesenchymal transition-related protein expression and led to marked downregulation of MAPK pathway-associated genes. Treatment with HI-TOPK-032 demonstrated therapeutic potential by suppressing aggressive cellular phenotypes and inducing apoptosis.
CONCLUSION
TOPK plays a critical role in pNEN progression and liver metastasis through the MAPK axis. HI-TOPK-032 exhibits promising antitumor activity by targeting TOPK, suggesting its potential as a therapeutic option for pNENs with liver metastasis. Further in vivo and clinical validation is warranted.
Core Tip: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare and typically slow growing but may lead to serious health complications. T-LAK cell-derived protein kinase is a serine/threonine kinase originally identified from a cDNA library of lymphokine-activated killer T cells and is overexpressed in multiple malignancies. This study demonstrates that T-LAK cell-derived protein kinase is markedly overexpressed in pNENs tissues with liver metastasis and further clarifies its effects on downstream signaling and the malignant biological behavior of pNENs.
