c-MET in Head and Neck Squamous Cell Carcinoma

Abstract

The kinase receptor c-MET (MET proto-oncogene, receptor tyrosine kinase; also known as the hepatocyte growth factor receptor) and its ligand hepatocyte growth factor/scatter factor (HGF/SF) are two promising, potentially therapeutically exploitable targets in head and neck squamous cell carcinoma (HNSCC). c-MET is commonly overexpressed in head and neck cancer cells compared to normal epithelial cells and HGF/SF is often detected at high expression levels in tumor-adjacent mesenchymal cells, inducing paracrine activation of c-MET to support tumor growth and proliferation. Blocking this paracrine activity has been shown to reduce the proliferative capacity of HNSCC cells. Importantly, c-MET signaling outputs intersect with those of multiple other signaling pathways that drive or otherwise contribute to HNSCC cell survival and spread, including EGFR, HER2, SRC, STAT3, PI3K, RAS, GRB2, and others. In this review, we emphasize the roles of c-MET and HGF in HNSCC as well as the potential for therapeutic targeting of this signaling axis.