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

• Published in: Molecular cancer 2022-01, Vol.21 (1), p.31-31, Article 31
• Main Authors: Raj, Sibi, Kesari, Kavindra Kumar, Kumar, Arun, Rathi, Brijesh, Sharma, Ashok, Gupta, Piyush Kumar, Jha, Saurabh Kumar, Jha, Niraj Kumar, Slama, Petr, Roychoudhury, Shubhadeep, Kumar, Dhruv
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Angiogenesis; Animals; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Biomarkers, Tumor; C-MET; c-Met protein; Cancer therapies; Cell cycle; Chemoresistance; Chemotherapy; Chromosomes; Clinical trials; Deoxyribonucleic acid; Disease; Disease Management; Disease Susceptibility; DNA; Drug Resistance, Neoplasm - genetics; EGFR; Energy Metabolism; Epidermal growth factor; FDA approval; Growth factors; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Head and neck squamous cell carcinoma; Hepatocellular carcinoma; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Human papillomavirus; Humans; Immunity; Immunomodulation; Invasiveness; Kinases; Larynx; Ligands; MAP kinase; Medical prognosis; Mesenchyme; Metastasis; Microenvironments; MicroRNAs; Monoclonal antibody; Morphogenesis; Motility; Pharynx; Phospholipase C; Phosphorylation; Physiology; Protein kinase; Proteins; Proto-Oncogene Proteins c-met - metabolism; Radiation; Review; Signal Transduction; Squamous cell carcinoma; Src protein; Threonine; Transcription factors; Treatment Outcome; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-022-01503-1

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.