Fig. 8
From: Identification of a novel anoikis signalling pathway using the fungal virulence factor gliotoxin
GT-induced anoikis signalling. FAK is recruited to focal adhesions via paxillin and is active in healthy adhesion cells. Active FAK phosphorylates p190RhoGAP. Phosphorylated p190RhoGAP stimulates the GTPase activity of RhoA. RhoA and the downstream anoikis-inducing cascade is therefore inactive (left). GT inactivates integrins, possibly by covalent binding to cysteines in the N-terminal region of α and β chains and triggers the disassembly of focal adhesions. Paxillin is degraded and FAK is inactivated, resulting in inactive p190RhoGAP. RhoA is consequently active and induces anoikis via a kinase cascade from ROCK to MKK4/MKK7 to JNK, resulting in the pro-apoptotic triple phosphorylation of Bim (right). Inhibitory integrin antibodies such as Cilengitide or FAK inhibitors such as FAK14 can induce the same anoikis signalling pathway
