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.
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.
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.
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.
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.
MET, a <i>c-met</i> proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis.
Interconversions between epithelial and mesenchymal states, often referred to as epithelial mesenchymal transition (EMT) and its reverse MET, play important roles in embryonic development and are recapitulated in various adult pathologies including cancer progression.
These findings suggest that c-MET overexpression in HA is not an early event in hepatocarcinogenesis, but constitutes a divergent molecular pathway leading to neoplastic change compared to overexpression observed in the late stages of tumour progression.
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.
The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy.
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.
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.
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.
However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic.
Aberrant activation of c-Met resulting from MET amplification and c-Met overexpression is associated with poor clinical outcome in multiple malignancies underscoring the importance of c-Met signaling in cancer progression.
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).
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.
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.