Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges

Figure 4 The HGF/c-MET signaling pathway and cancer stemness. In the absence of the HGF ligand, the HGF/c-MET pathway remains inactivated. The binding of the HGF ligand to the c-MET kinase receptor results in the dimerization of two subunits that further leads to auto-phosphorylation of the tyrosine residues in the cytoplasmic domain of the receptor creating a docking site for adaptor proteins, which regulate pathways, such as PI3K, RAS, Wnt, Notch and STAT pathway. Transcriptional levels of c-MET were high in ALDH^high cells[70]. Activation of c-MET results in an increase in invasiveness and metastasis in vitro as well as in vivo[73,74]. Ficlatuzumab is a humanized IgG1 monoclonal antibody targeting HGF used to therapeutically target the HGF/c-met pathway. ALDH: Aldehyde dehydrogenase; Ficlatuzumab: HGF/c-MET pathway inhibitor.