c-Met (MET) in various biological processes and different diseases

Target Name: MET

NCBI ID: G4233

Content of Review Report on MET Target / Biomarker

MET

c-Met (MET) in various biological processes and different diseases

In hepatoblastoma (HB), mutant beta-catenin escapes degradation and enters the nucleus, activating the transcription of target genes. Additionally, HB tumor cells can suppress beta-catenin degradation through CAPRIN2-activating mutations, leading to beta-catenin accumulation. Notably, c-Met activation by hepatocyte growth factor (HGF) induces beta-catenin translocation to the nucleus via tyrosine phosphorylation. Studies have shown a positive correlation between activated c-Met and nuclear accumulation of beta-catenin in human HB specimens.

In melanoma, c-MET can be upregulated through transcriptional regulation by MITF and reduced levels of miRNAs targeting c-MET transcript. Elevated levels of HGF, produced by both stromal cells and melanoma cells, enhance c-MET activity, contributing to melanoma progression. Autocrine HGF/c-MET signaling supports melanoma cell proliferation, survival, motility, invasiveness, and niche formation.

In a study utilizing JNJ-61186372 BsAb, it was found that high EGFR to c-MET expression confers increased potency in blocking HGF-mediated phosphorylation, highlighting the role of c-MET in target engagement.

MET amplification has been associated with EGFR-TKI resistance in certain cancers. It activates EGFR-independent phosphorylation of ErbB3, leading to downstream activation of the PI3K/AKT pathway, which bypasses the effects of EGFR-TKI.

Lnc-TALC, a long non-coding RNA (lncRNA), exerts its effect on glioblastoma (GBM) by regulating the c-Met signaling pathway as a competitive RNA. The mechanistic scheme of lnc-TALC involves promoting MGMT expression, potentially serving as a therapeutic target to overcome resistance to TMZ chemotherapy in GBM patients.

Overall, c-Met (MET) has been implicated in various disease contexts, modulating biological processes, drug resistance, and potential therapeutic targets.

Targeting the HGF/c-MET interaction could be effective in countering microenvironment-driven support to leukemic cells. Combinatorial therapies utilizing conventional drugs along with c-MET kinase inhibitors or exosomes-delivered effector molecules could enhance therapeutic approaches.

Loss of ABHD5 releases DPY30 to translocate into the nucleus, leading to increased YAP methylation and activation. This promotes the transcription of c-Met, contributing to the development and progression of colorectal cancers.

FCHSD2 regulates multiple steps in endocytic trafficking and alters downstream signaling of receptor tyrosine kinases (RTKs). Loss of FCHSD2 leads to the accumulation of RTKs in late endosomes/lysosomes and enhances the transcription and expression of c-Jun, EGFR, and c-Met. The expression of FCHSD2 is decreased in higher grades of lung adenocarcinoma tumors, and patients with higher FCHSD2 expression have better survival rates.

In summary, targeting the HGF/c-MET interaction and the regulation of c-MET expression through ABHD5 and FCHSD2 have potential implications for therapeutic interventions in CLL and colorectal and lung cancers, respectively .

Protein Name: MET Proto-oncogene, Receptor Tyrosine Kinase

Functions: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity)

The "MET Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about MET comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets