• ARS
• Alternative RNA splicing
• Cirrhosis
• Exon skipping
• Hepatocellular carcinoma
• Hepatoma
• Intron retention
• NAFLD
• NASH
• RNA processing
• RNA splicing
• RNA-Seq
• Spliceosome
• Splicing factors
• Transcript variants

• Alternative Splicing
• Carcinoma, Hepatocellular/genetics
• Humans
• Introns
• Liver Neoplasms/genetics
• Protein Isoforms/genetics
• RNA Splice Sites

• TAR/2018/001054 Science and Engineering Research Board
• 5/13/38/2014-NCD-III Indian Council of Medical Research
• 5/13/55/2020/NCD-III Indian Council of Medical Research
• 5/13/4/ACB/ICRC/2020/NCD-III Indian Council of Medical Research

MST1R/RON receptor tyrosine kinase is a highly conserved transmembrane protein present on epithelial cells, macrophages, and recently identified in a T-cell subset. RON activation attenuates inflammation in healthy tissue. Interestingly, it is overexpressed in several epithelial neoplasms with increasing levels of expression associated with worse outcomes. Though the mechanisms involved are still under investigation, RON is involved in carcinogenesis via immune modulation of the immune tumor microenvironment, activation of numerous oncogenic pathways, and is protective under cellular stress. Alternatively, inhibition of RON abrogates tumor progression in both animal and human tissue models. Given this, RON is a targetable protein of great interest for cancer treatment. Here, we review RON’s function in tissue inflammation and cancer progression, and review cancer clinical trials to date that have used agents targeting RON signaling.

The MST1R/RON receptor tyrosine kinase is a homologue of the more well-known MET receptor. Like MET, RON orchestrates cell signaling pathways that promote oncogenesis and enable cancer cell survival; however, it has a more unique role in the regulation of inflammation. RON was originally described as a transmembrane receptor expressed on tissue resident macrophages and various epithelial cells. RON is overexpressed in a variety of cancers and its activation modifies multiple signaling pathways with resultant changes in epithelial and immune cells which together modulate oncogenic phenotypes. While several RON isoforms have been identified with differences in structure, activation, and pathway regulation, increased RON expression and/or activation is consistently associated with worse outcomes. Tyrosine kinase inhibitors targeting RON have been developed, making RON an actionable therapeutic target.

• MET
• MST1R
• RON
• cancer
• tyrosine kinase

• CA155620 NIH HHS

The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family. Research has shown that RON has a role in cancer pathogenesis, which places RON on the frontline of the development of novel cancer therapeutic strategies. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death. Therefore, to combat these malignant diseases, the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis, and the development of RON as a drug target for therapeutic intervention should be investigated. Abnormal RON expression and signaling have been identified in HBP cancers, and also act as tumorigenic determinants for HBP cancer malignant behaviors. In addition, RON is emerging as an important mediator of the clinical prognosis of HBP cancers. Thus, not only is RON significant in HBP cancers, but also RON-targeted therapeutics could be developed to treat these cancers, for example, therapeutic monoclonal antibodies and small-molecule inhibitors. Among them, antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.

• RON
• Signal transduction
• Hepatobiliary
• Pancreatic neoplasms
• Molecular targeted therapy

• Humans
• Antibodies, Monoclonal
• Immunoconjugates
• Pancreatic Neoplasms/drug therapy
• Proto-Oncogene Mas
• Signal Transduction

As the sixth most lethal cancers worldwide, hepatocellular carcinoma (HCC) has been treated with doxorubicin (Dox) for decades. However, chemotherapy resistance, especially for Dox is an even more prominent problem due to its high cardiotoxicity. To find a regimen to reduce Dox resistance, and identify the mechanisms behind it, we tried to identify combination of drugs that can overcome drug resistance by screening tyrosine kinase inhibitor(s) with Dox with various HCC cell lines in vitro and in vivo. We report here that combination of Crizo and Dox has a synergistic effect on inducing HCC cell death. Accordingly, Crizo plus Dox increases Dox accumulation in nucleus 3-16 times compared to Dox only; HCC cell death enhanced at least 50% in vitro and tumor weights reduced ranging from 35 to 65%. Combining these two drugs reduces multiple drug resistance 1 (MDR1) protein as a result of activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), which phosphorylates eIF2α, leading to protein translational repression. Additionally, PERK stimulation activates C-Jun terminal kinase (JNK), resulting in accumulation of unfused autophagosome to enhance autophagic cell death via Poly-ADP-ribosyltransferase (PARP-1) cleavage. When the activity of PERK or JNK is blocked, unfused autophagosome is diminished, cleaved PARP-1 is reduced, and cell death is abated. Therefore, Crizo plus Dox sensitize HCC drug resistance by engaging PERK-p- eIF2α-MDR1, and kill HCC cells by engaging PERK-JNK- autophagic cell death pathways. These newly discovered mechanisms of Crizo plus Dox not only provide a potential treatment for HCC but also point to an approach to overcome MDR1 related drug resistance in other cancers.

• ER stress
• PERK
• autophagic cell death
• hepatocellular carcinoma
• multi-drug resistant protein 1

Metabolic diseases, such as diabetes, obesity, and fatty liver disease, have now reached epidemic proportions. Receptor tyrosine kinases (RTKs) are a family of cell surface receptors responding to growth factors, hormones, and cytokines to mediate a diverse set of fundamental cellular and metabolic signaling pathways. These ligands signal by endocrine, paracrine, or autocrine means in peripheral organs and in the central nervous system to control cellular and tissue-specific metabolic processes. Interestingly, the expression of many RTKs and their ligands are controlled by changes in metabolic demand, for example, during starvation, feeding, or obesity. In addition, studies of RTKs and their ligands in regulating energy homeostasis have revealed unexpected diversity in the mechanisms of action and their specific metabolic functions. Our current understanding of the molecular, biochemical and genetic control of energy homeostasis by the endocrine RTK ligands insulin, FGF21 and FGF19 are now relatively well understood. In addition to these classical endocrine signals, non-endocrine ligands can govern local energy regulation, and the intriguing crosstalk between the RTK family and the TGFβ receptor family demonstrates a signaling network that diversifies metabolic process between tissues. Thus, there is a need to increase our molecular and mechanistic understanding of signal diversification of RTK actions in metabolic disease. Here we review the known and emerging molecular mechanisms of RTK signaling that regulate systemic glucose and lipid metabolism, as well as highlighting unexpected roles of non-classical RTK ligands that crosstalk with other receptor pathways.

• glucose
• lipids
• metabolism
• receptor tyrosine kinases
• signaling

• IMC-RON8
• Macrophage-stimulating protein receptor
• Narnatumab
• Phase 1
• RON
• Solid tumors

• Cancer
• Drug conjugate
• Monoclonal antibody
• Peptide
• Target therapy
• Tumor
• Tyrosine kinase receptor

• Animals
• Antineoplastic Agents/therapeutic use
• Drug Delivery Systems/methods
• Humans
• Molecular Targeted Therapy/methods
• Neoplasms/drug therapy
• Neoplasms/genetics
• Protein Domains/genetics
• Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
• Receptor Protein-Tyrosine Kinases/chemistry
• Receptor Protein-Tyrosine Kinases/genetics

• MET
• MET-targeted therapy
• amplification
• biomarker
• overexpression

• Antibodies, Monoclonal/therapeutic use
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents/therapeutic use
• Benzamides
• Biomarkers, Tumor/antagonists & inhibitors
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinogenesis/metabolism
• Cell Movement
• Cell Proliferation
• Cell Transformation, Neoplastic
• Clinical Trials as Topic
• Gene Amplification
• Hepatocyte Growth Factor/metabolism
• Humans
• Imidazoles/therapeutic use
• Molecular Targeted Therapy/methods
• Mutation
• Neoplasms/drug therapy
• Neoplasms/pathology
• Patient Selection
• Protein Kinase Inhibitors/therapeutic use
• Proto-Oncogene Proteins c-met/antagonists & inhibitors
• Proto-Oncogene Proteins c-met/genetics
• Proto-Oncogene Proteins c-met/metabolism
• Pyrazines/therapeutic use
• Signal Transduction
• Triazines/therapeutic use

Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.

• HGF
• HGFA
• MSP
• RON
• breast cancer
• c-MET
• cell signaling
• growth factor
• hepsin
• inhibitor
• ketothiazole
• kinase
• matriptase
• peptidomimetic
• serine protease
• solid-phase peptide synthesis

• Cell signaling
• Hepatocarcinogenesis
• MSPR/RON
• Receptor tyrosine kinase
• Small leucine-rich proteoglycan
• c-Myc
• β-Catenin

Ron is a human receptor for the macrophage-stimulating protein (MSP). Exon 11 skipping of Ron pre-mRNA produces the RonΔ165 protein that has a deletion of a 49 amino acid region in the β-chain extracellular domain. RonΔ165 is constitutively active even in the absence of its ligand. Through stepwise deletion analysis, we identified a 2-nt RNA enhancer, which is located 74 nt upstream from the 5′ splice site of exon 11, for exon 11 inclusion. Through double-base and single-base substitution analysis of the 2-nt RNA, we demonstrated that the GA, CC, UG and AC dinucleotides on exon 11, in addition to the wild-type AG sequence, function as enhancers for exon 11 inclusion of the Ron pre-mRNA.

The RON gene encodes a tyrosine kinase receptor for macrophage-stimulating protein. A constitutively active isoform that arises by skipping of exon 11 is expressed in carcinomas and contributes to an invasive phenotype. However, a high proportion of the mRNA expressed from the endogenous gene, or from transfected minigenes, appears to retain introns 10 and 11. It is not known whether this represents specific repression or the presence of weak splicing signals. We have used chimeric pre-mRNAs spliced in vitro to investigate the reason for intron retention. A systematic test showed that, surprisingly, the exon sequences known to modulate exon 11 skipping were not limiting, but the 3’ splice site regions adjacent to exons 11 and 12 were too weak to support splicing when inserted into a globin intron. UV-crosslinking experiments showed binding of hnRNP F/H just 5’ of these regions, but the hnRNP F/H target sequences did not mediate inhibition. Instead, the failure of splicing is linked to weak binding of U2AF65, and spliceosome assembly stalls prior to formation of any of the ATP-dependent complexes. We discuss mechanisms by which U2AF65 binding is facilitated in vivo.

• Alternative Splicing/genetics
• Base Sequence
• Consensus Sequence
• Cross-Linking Reagents/pharmacology
• HeLa Cells
• Humans
• Introns/genetics
• Molecular Sequence Data
• Protein Binding
• RNA Splice Sites/genetics
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Receptor Protein-Tyrosine Kinases/genetics
• beta-Globins/genetics

• Medical Research Council

Although EGFR inhibitors have shown some success in the treatment of head and neck squamous cell carcinomas (HNSCCs), the results are not dramatic. Additional molecular targets are urgently needed. We previously showed that the loss of Ron receptor activity significantly slowed squamous tumour growth and progression in a murine model. Based on these data, we hypothesised that Ron expression confers an aggressive phenotype in HNSCCs.

We prospectively collected and evaluated 154 snap-frozen, primary HNSCCs for Ron and EGFR expression/phosphorylation. Biomarker correlation with clinical, pathological and outcome data was performed. The biological responses of HNSCC cell lines to Ron knockdown, its activation and the biochemical interaction between Ron and EGFR were examined.

We discovered that 64.3% (99 out of 154) HNSCCs expressed Ron. The carcinomas expressed exclusively mature functional Ron, whereas the adjacent nonmalignant epithelium expressed predominantly nonfunctional Ron precursor. There was no significant association between Ron and sex, tumour differentiation, perineural/vascular invasion or staging. However, patients with Ron+HNSCC were significantly older and more likely to have oropharyngeal tumours. Ron+HNSCC also had significantly higher EGFR expression and correlated strongly with phosphorylated EGFR (pEGFR). Newly diagnosed HNSCC with either Ron/pEGFR or both had lower disease-free survival than those without Ron and pEGFR. Knocking down Ron in SCC9 cells significantly blunted their migratory response to not only the Ron ligand, MSP, but also EGF. Stimulation of Ron in SCC9 cells significantly augmented the growth effect of EGF; the synergistic effect of both growth factors in SCC9 cells was dependent on Ron expression. Activated Ron also interacted with and transactivated EGFR.

Ron synergises with EGFR to confer certain adverse features in HNSCCs.

Increasing evidence suggests that miRNAs have a profound impact on host defense to Hepatitis C virus (HCV) infection and clinical outcome of standard HCV therapy. In this study, we investigated modulation of miRNA expression in Huh7.5 hepatoma cells by HCV infection and in vitro interferon-αtreatment.

MiRNA expression profiling was determined using Human miRNA TaqMan® Arrays followed by rigorous pairwise statistical analysis. MiRNA inhibitors assessed the functional effects of miRNAs on HCV replication. Computational analysis predicted anti-correlated mRNA targets and their involvement in host cellular pathways. Quantitative RTPCR confirmed the expression of predicted miRNA-mRNA correlated pairs in HCV-infected Huh7.5 cells with and without interferon-α.

Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-α treatment (p<0.01). The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection.

HCV differentially modulates miRNAs to facilitate entry and early establishment of infection in vitro. Interferon-α appears to neutralize the effect of HCV replication on miRNA regulation thus providing a potential mechanism of action in eradicating HCV from hepatocytes.

Human RON (Recepteur d’Origine Nantais) receptor tyrosine kinase is a cell surface receptor for Macrophage Stimulating Protein (MSP). RON mediates signal transduction pathways that regulate cell adhesion, invasion, motility and apoptosis processes. Elevated levels of RON and its alternatively spliced variants are implicated in the progression and metastasis of tumor cells. The binding of MSP α/β heterodimer to the extracellular region of RON receptor induces receptor dimerization and activation by autophosphorylation of the intracellular kinase domains. The ectodomain of RON, containing the ligand recognition and dimerization domains, is composed of a semaphorin (Sema), Plexins-Semaphorins-Integrins domain (PSI), and four Immunoglobulins-Plexins-Transcription factor (IPT) domains. High affinity association between MSP and RON is mediated by the interaction between MSP β-chain and RON Sema, although RON activation requires intact RON and MSP proteins. Here, we report the structure of RON Sema-PSI domains at 1.85 Å resolution. RON Sema domain adopts a seven-bladed β-propeller fold, followed by disulfide bond rich, cysteine-knot PSI motif. Comparison with the homologous Met receptor tyrosine kinase reveals that RON Sema-PSI contains distinguishing secondary structural features. These define the receptors’ exclusive selectivity towards their respective ligands, RON for MSP and Met for HGF. The RON Sema-PSI crystal packing generates a homodimer with interface formed by the Sema domain. Mapping of the dimer interface using the RON homology to Met, MSP homology to Hepatocyte Growth Factor (HGF), and the structure of the Met/HGF complex shows the dimer interface overlapping with the putative MSPβ binding site. The crystallographically determined RON Sema-PSI homodimer may represent the dimer assembly that occurs during ligand-independent receptor activation and/or the inhibition of the constitutive activity of RONΔ160 splice variant by the soluble RON splice variant, RONΔ85.

• ron
• mst1r
• met
• msp
• hgf
• stat3
• stomach cancer
• gastroesophageal adenocarcinoma
• r1018g mutation

• Adenocarcinoma/genetics
• Adenocarcinoma/metabolism
• Adenocarcinoma/mortality
• Cell Line, Tumor
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/mortality
• Gene Dosage
• Hepatocyte Growth Factor/metabolism
• Humans
• In Situ Hybridization, Fluorescence
• Indoles/pharmacology
• Mutation
• Piperazines/pharmacology
• Prognosis
• Protein Kinase Inhibitors/pharmacology
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-met/antagonists & inhibitors
• Proto-Oncogene Proteins c-met/genetics
• Proto-Oncogene Proteins c-met/metabolism
• RNA, Small Interfering
• Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
• Receptor Protein-Tyrosine Kinases/genetics
• Receptor Protein-Tyrosine Kinases/metabolism
• Receptor, ErbB-2/genetics
• Receptors, Growth Factor/antagonists & inhibitors
• Receptors, Growth Factor/genetics
• Receptors, Growth Factor/metabolism
• STAT3 Transcription Factor/antagonists & inhibitors
• STAT3 Transcription Factor/metabolism
• Signal Transduction
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/mortality
• Sulfonamides/pharmacology

• 5R01CA129501-03 NCI NIH HHS
• T32 CA009566 NCI NIH HHS
• 5R01CA125541-04 NCI NIH HHS
• 5R01CA10075007 NCI NIH HHS
• 3R01CA129501-02S1 NCI NIH HHS
• 1R21CA140003-01 NCI NIH HHS
• 3R01CA125541-03S1 NCI NIH HHS

• Alternative Splicing/drug effects
• Alternative Splicing/genetics
• Amiloride/chemistry
• Amiloride/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Nucleus/drug effects
• Cell Nucleus/metabolism
• Cytokinesis/drug effects
• Cytoskeleton/metabolism
• DNA Fragmentation/drug effects
• DNA Repair/drug effects
• Enzyme Activation/drug effects
• Exons/genetics
• Gene Expression Regulation, Neoplastic/drug effects
• Genes, Neoplasm/genetics
• Genome, Human/genetics
• Humans
• Mitosis/drug effects
• Neoplasm Invasiveness
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Neoplasms/genetics
• Neoplasms/pathology
• Nuclear Proteins/metabolism
• Phosphorylation/drug effects
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• Protein Phosphatase 1/metabolism
• Proteomics
• Proto-Oncogene Proteins c-akt/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• RNA-Binding Proteins/metabolism
• Serine-Arginine Splicing Factors

• Animals
• Cell Transformation, Neoplastic/metabolism
• Hepatocyte Growth Factor/metabolism
• Humans
• Mice
• Neoplasm Metastasis
• Oncogenes
• Proto-Oncogene Proteins/metabolism
• Receptor Protein-Tyrosine Kinases/metabolism

• CA-111819 NCI NIH HHS
• R01 CA125379 NCI NIH HHS
• K08 CA111819 NCI NIH HHS
• CA-100002 NCI NIH HHS
• DK-064403 NIDDK NIH HHS
• R24 DK064403 NIDDK NIH HHS
• R01 CA100002 NCI NIH HHS
• R01 DK073552 NIDDK NIH HHS
• DK-073552 NIDDK NIH HHS

• Animals
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/pharmacology
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Movement/immunology
• HT29 Cells
• Hepatocyte Growth Factor/antagonists & inhibitors
• Hepatocyte Growth Factor/metabolism
• Humans
• Immunoglobulin Fragments/immunology
• Immunoglobulin G/immunology
• Immunoglobulin G/pharmacology
• Mice
• Mitogen-Activated Protein Kinases/antagonists & inhibitors
• Mitogen-Activated Protein Kinases/metabolism
• NIH 3T3 Cells
• Peptide Library
• Phosphorylation
• Proto-Oncogene Proteins/antagonists & inhibitors
• Proto-Oncogene Proteins/metabolism
• Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
• Receptor Protein-Tyrosine Kinases/immunology
• Receptor Protein-Tyrosine Kinases/metabolism
• Xenograft Model Antitumor Assays

Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.

• Biomarkers, Tumor/analysis
• Carcinoma, Transitional Cell/genetics
• Carcinoma, Transitional Cell/pathology
• Cohort Studies
• Gene Expression Profiling
• Hepatocyte Growth Factor
• Humans
• Immunohistochemistry
• Macrophages
• Polymerase Chain Reaction
• Prognosis
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-met/biosynthesis
• Proto-Oncogene Proteins c-met/genetics
• Receptor Protein-Tyrosine Kinases/biosynthesis
• Receptor Protein-Tyrosine Kinases/genetics
• Survival Analysis
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/pathology

• Animals
• Blotting, Western
• Disease Models, Animal
• Female
• Immunohistochemistry
• Inbreeding
• Male
• Mammary Neoplasms, Experimental/enzymology
• Mammary Neoplasms, Experimental/pathology
• Mice
• Mice, Knockout
• Neoplasm Metastasis
• Protein Serine-Threonine Kinases/metabolism
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-akt
• Receptor Protein-Tyrosine Kinases/deficiency
• Receptor Protein-Tyrosine Kinases/physiology
• Signal Transduction

• R01 CA100002-02 NCI NIH HHS
• R01 CA100002-05 NCI NIH HHS
• R01 CA100002-03 NCI NIH HHS
• HD36888 NICHD NIH HHS
• T-32-HL07752 NHLBI NIH HHS
• R01 CA100002 NCI NIH HHS
• CA100002 NCI NIH HHS
• R01 CA100002-01A1 NCI NIH HHS
• R01 CA100002-04 NCI NIH HHS

• Animals
• Cell Transformation, Neoplastic/pathology
• Disease Models, Animal
• Humans
• Kinetics
• Mice
• Mice, Transgenic
• Papilloma/pathology
• Receptor Protein-Tyrosine Kinases/deficiency
• Receptor Protein-Tyrosine Kinases/genetics
• Receptor Protein-Tyrosine Kinases/physiology
• Signal Transduction
• Skin Neoplasms/pathology
• Skin Neoplasms/prevention & control

• R01 CA100002-02 NCI NIH HHS
• R01 HD036888-05 NICHD NIH HHS
• R01 HD036888 NICHD NIH HHS
• R01 HD036888-04 NICHD NIH HHS
• T32 HD43005-01 NICHD NIH HHS
• R01 CA100002-03 NCI NIH HHS
• T32 HD043005 NICHD NIH HHS
• R01 CA100002 NCI NIH HHS
• R01 CA100002-01A1 NCI NIH HHS
• HD-36888 NICHD NIH HHS

• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• DNA Methylation
• Disease Progression
• Forecasting
• Gene Expression Regulation, Neoplastic
• Hepatitis/complications
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Loss of Heterozygosity
• Models, Genetic
• Neoplasm Metastasis
• Risk Factors

• CA 48656 NCI NIH HHS
• CA 66971 NCI NIH HHS
• CA 79512 NCI NIH HHS

• 3T3 Cells
• Amino Acid Sequence
• Animals
• Blotting, Western
• Carcinoma/genetics
• Cell Division
• Cell Transformation, Neoplastic
• DNA, Complementary/metabolism
• Growth Substances/metabolism
• Hepatocyte Growth Factor
• Humans
• Kidney Neoplasms/genetics
• Ligands
• Lung Neoplasms/genetics
• Lung Neoplasms/secondary
• Mice
• Molecular Sequence Data
• Mutation
• Neoplasm Metastasis
• Neoplasms/genetics
• Phosphorylation
• Point Mutation
• Protein Binding
• Protein Structure, Tertiary
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• RNA/metabolism
• Receptor Protein-Tyrosine Kinases/genetics
• Receptor Protein-Tyrosine Kinases/metabolism
• Receptor Protein-Tyrosine Kinases/physiology
• Receptors, Cell Surface/genetics
• Receptors, Cell Surface/metabolism
• Receptors, Cell Surface/physiology
• Sequence Homology, Amino Acid
• Transfection
• Tumor Cells, Cultured

• DK-47003 NIDDK NIH HHS
• DK-58182 NIDDK NIH HHS
• HD-36888 NICHD NIH HHS
• T32-HL-07752 NHLBI NIH HHS

• 5' Untranslated Regions/physiology
• Animals
• Antineoplastic Agents/pharmacology
• Binding Sites/genetics
• Carcinoma, Hepatocellular
• Curcumin/pharmacology
• Gene Expression Regulation, Neoplastic/drug effects
• Hepatocyte Growth Factor/antagonists & inhibitors
• Hepatocyte Growth Factor/physiology
• Humans
• Ligands
• Mice
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-met/antagonists & inhibitors
• Proto-Oncogene Proteins c-met/biosynthesis
• Proto-Oncogene Proteins c-met/genetics
• Proto-Oncogene Proteins c-met/metabolism
• RNA, Messenger/antagonists & inhibitors
• RNA, Messenger/biosynthesis
• Sp1 Transcription Factor/metabolism
• Transcription Factor AP-1/biosynthesis
• Transcription Factor AP-1/physiology
• Transcriptional Activation/drug effects
• Tumor Cells, Cultured

• Alternative Splicing
• Animals
• Carcinogens
• DNA/biosynthesis
• Diethylnitrosamine
• Female
• Hepatocyte Growth Factor/classification
• Hepatocyte Growth Factor/genetics
• Hepatocyte Growth Factor/physiology
• Liver/metabolism
• Liver Neoplasms, Experimental/chemically induced
• Liver Neoplasms, Experimental/etiology
• Liver Neoplasms, Experimental/genetics
• Male
• Mice
• Mice, Transgenic
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Proto-Oncogene Proteins c-met/genetics
• Proto-Oncogene Proteins c-met/metabolism
• RNA, Messenger/metabolism
• Sequence Deletion
• Sex Factors

• R01ES06109 NIEHS NIH HHS