Proto-Oncogene c-Met: A Core Regulator in Development, Cancer, and Targeted Therapy

Proto-Oncogene c-Met: A Core Regulator in Development, Cancer, and Targeted Therapy

Proto-Oncogene c-Met: A Core Regulator in Development, Cancer, and Targeted Therapy

Knowledge Overview · Research Tools · Powered by ANT BIO PTE. LTD.

1. Core Concept

c-Met (also known as Hepatocyte Growth Factor Receptor, HGFR) is a high‑affinity receptor tyrosine kinase (RTK) encoded by the MET proto‑oncogene. It is the only known receptor for Hepatocyte Growth Factor (HGF). The HGF/c-Met axis governs cell proliferation, survival, migration, invasion, morphogenesis, and angiogenesis. Under physiological conditions, it supports embryonic development and tissue repair; when dysregulated, it drives oncogenic transformation, metastasis, and drug resistance.

2. Latest Research Frontiers

Recent advances have redefined c-Met as a versatile therapeutic and diagnostic target:

  • Structural biology reveals full‑length c-Met dimerization and activation conformations.
  • c-Met drives cancer progression via amplification, mutations, exon 14 skipping, and stromal crosstalk.
  • It signals from endosomes and even the nucleus, expanding its functional scope.
  • c-Met mediates resistance to EGFR, HER2, and immune checkpoint therapies.
  • Soluble c-Met (sMET) serves as a noninvasive biomarker for tumor monitoring.
  • Novel modalities include c-Met–targeted ADCs, bispecific antibodies, and PROTACs.

3. Research Significance

c-Met is a pivotal molecule in both physiology and pathology:

  • Essential for liver, placenta, muscle, and neuron development.
  • Promotes tissue regeneration after acute injury.
  • A validated oncogenic driver in lung, gastric, liver, renal, and other solid tumors.
  • Strongly correlated with cancer invasion, metastasis, and poor prognosis.
  • A proven clinical target for targeted therapy and companion diagnostics.

4. Molecular Mechanism & Research Applications

4.1 Structural and Signaling Mechanism

c-Met forms a disulfide‑linked heterodimer composed of an α‑chain and a β‑chain.

  • Extracellular region: SEMA, PSI, and IPT domains responsible for HGF binding.
  • Intracellular region: tyrosine kinase (TK) domain and multisubstrate docking sites.
  • HGF binding induces dimerization and autophosphorylation at Y1234/Y1235 and Y1349/Y1353.
  • Downstream pathways include PI3K‑AKT, RAS‑MAPK, STAT, and NF‑κB.
  • The adaptor protein Gab1 mediates more than 80% of c-Met signaling output.

 

4.2 Physiological Functions

  • Embryonic development: hepatoblast migration, placentation, motor neuron guidance.
  • Tissue homeostasis: epithelial repair, liver regeneration, angiogenesis.
  • Stem cell regulation: maintenance and differentiation of tissue progenitor cells.

4.3 Pathological Roles in Cancer

  • Gene amplification in gastric, esophageal, and NSCLC.
  • Activating mutations in hereditary and sporadic renal cancers.
  • Exon 14 skipping leads to protein stabilization and constitutive activity.
  • Promotes EMT, invasion, metastasis, and cancer stem cell maintenance.
  • Induces resistance to EGFR inhibitors and immunotherapy.

4.4 Therapeutic Strategies

  • Small‑molecule tyrosine kinase inhibitors (crizotinib, capmatinib, tepotinib).
  • Anti‑c-Met and anti‑HGF neutralizing antibodies.
  • Antibody‑drug conjugates (ADCs) for targeted tumor killing.
  • Bispecific T‑cell engagers and immunotherapy combinations.
  • Biomarker‑driven patient stratification: MET amplification, exon 14 skipping.

4.5 Non-Oncological Applications

  • Liver injury repair and regeneration.
  • Cardioprotection and ischemic angiogenesis.
  • Neuroprotection and synaptic maintenance.
  • Tissue engineering and stem cell culture supplements.

5. Our Mission at ANT BIO PTE. LTD.

ANT BIO PTE. LTD. provides high‑quality reagents to accelerate global research in signal transduction, oncology, and regenerative medicine. Our portfolio includes recombinant proteins, antibodies, ELISA kits, and general reagents optimized for c-Met/HGF axis research.

Our three specialized sub‑brands support your full research cycle:

  • Absin: Detection kits and general laboratory reagents.
  • Starter: Highly validated antibodies for WB, IHC, IF, and IP.
  • UA: Bioactive recombinant proteins for functional assays.

Featured Related Products from ANT BIO PTE. LTD.

Recombinant Proteins (UA Brand)

  • Human c-Met (HGFR) recombinant protein
  • Human HGF recombinant protein (active)
  • Human Gab1 recombinant protein
  • Mouse HGF recombinant protein
  • Phosphorylated kinase control proteins

Antibodies (Starter Brand)

  • Anti–c-Met rabbit monoclonal antibody
  • Anti–phospho-c-Met (Y1234/Y1235) antibody
  • Anti-HGF antibody
  • Anti-Gab1 antibody
  • Anti–MET exon 14 skipping variant antibody

Kits & General Reagents (Absin Brand)

  • Human c-Met ELISA Kit
  • Human HGF ELISA Kit
  • c-Met kinase activity assay kit
  • Western blot lysis buffer and enhancer reagents

Brand Promotion

ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights