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.

Amity Institute of Molecular and Stem Cell Research Amity University Uttar Pradesh Noida 201313 India

Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno Brno Czech Republic

Department of Applied Physics School of Science Aalto University 00076 Espoo Finland

Department of Biochemistry All India Institute of Medical Science Ansari Nagar New Delhi Bharat 110029 India

Department of Biotechnology School of Engineering and Technology Sharda University Greater Noida UP 201310 India

Department of Life Science and Bioinformatics Assam University Silchar 788011 India

Department of Life Sciences School of Basic Sciences and Research Sharda University Greater Noida 201310 India

Laboratory for Translational Chemistry and Drug Discovery Department of Chemistry Hansraj College University of Delhi Delhi India

Mahavir Cancer Institute and Research Center Phulwarisharif Patna Bihar 801505 India

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