Overexpression of hepatocyte growth factor and Met and mutations and amplification of MET have been noted in many forms of cancer and are reportedly correlated with cancer progression and a poor prognosis.
To investigate how elevated stromal tRNAi(Met) contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi(Met) gene (2+tRNAi(Met) mouse).
These results identify multiple regions of MET responsible for HGF-mediated tumor progression, unraveling the complexity of HGF-MET interaction, and provide selective molecular tools for targeting MET activity in cancer.
These findings reveal the therapeutic potential of targeting the HGF/MET pathway for inhibition, to constrain tumor progression of SCLC cells showing aberrant activation of HGF/MET signaling.
Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy.
Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.
These studies also demonstrate that mutationally activated MET plays a significant role in a wide range of cancers and RTKs can promote tumor progression through diverse mechanisms.
The MET and RON receptors are tyrosine kinases that form a non-covalent complex on the cell surface that functions in several steps of tumor progression.
Increased activity of these and the plasma protease, hepatocyte growth factor activator (HGFA), is associated with unregulated cell signaling and tumor progression through increased MET and RON kinase signaling pathways.
This review shows a molecular aspect of NSCLC biomarkers used in clinical approaches, such as EGFR, KRAS, MET, indicating mutations that are crucial for cancer progression and related to treatment properties.
The role of aberrant hepatocyte growth factor receptor (c-MET, also known as tyrosine-protein kinase MET)/hepatocyte growth factor (HGF) signaling in cancer progression and invasion has been extensively studied. c-MET inhibitors have shown promising pre-clinical and early phase clinical trial anti-tumor activity in several tumor types, although results of most phase III trials with these agents have been negative.
Median time to tumor progression was 2.3 months (range, 0.4-19.7) for all treated patients with no responses in patients with a MET abnormality or single-agent c-MET inhibitor treatment.
MET could serve as a biomarker for the prognostication of patients with clear-cell adenocarcinoma and tumor progression, and has potential as a novel therapeutic target for this carcinoma.
Activation of hepatocyte growth factor (HGF) by proteolytic processing is triggered in cancer microenvironments, and subsequent signaling through the MET receptor is involved in cancer progression.
EGF receptor (EGFR) and MET (the receptor tyrosine kinase for hepatocyte growth factors) are cell-surface tyrosine kinase receptors that have been implicated in diverse cellular processes and as regulators of several microRNAs (miRNAs), thus contributing to tumor progression.
C-MET and phospho-MET overexpression occurred preferentially in ADCs and in areas involved in tumor progression, in support of the view that MET activation plays a role in the development of an invasive phenotype in NSCLC.