Fig. 9.

Stimuli driving c-Met/β1 complex formation promote ligand-independent cross-activation of each receptor and enhance cancer cell invasion. (A) Biologic and therapeutic stimuli (metastases, bevacizumab resistance, HGF, and hypoxia) promote c-Met/β1 integrin complex formation, which maintains β1 integrin in its activate state even without fibronectin (FN), with the c-Met/β1 complex exhibiting greater FN affinity than β1 bound to its conventional heterodimer partners αV or α5. (B) Stimuli described in A promote c-Met/β1 complex formation, with the c-Met/β1 complex exhibiting greater affinity for FN than β1 bound to its α-heterodimer partners and FN promoting ILK-mediated c-Met phosphorylation even in the absence of HGF.