Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer

Mol Cancer. 2022 Jan 26;21(1):31. doi: 10.1186/s12943-022-01503-1.

Abstract

Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.

Keywords: C-MET; Chemoresistance; EGFR; Head and neck squamous cell carcinoma; Hepatocyte growth factor; Monoclonal antibody.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Disease Management
  • Disease Susceptibility
  • Drug Resistance, Neoplasm / genetics
  • Energy Metabolism
  • Head and Neck Neoplasms / etiology*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Immunity
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction*
  • Treatment Outcome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • HGF protein, human
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met