Fig. (8).

Schematic representation of integrin activation states and signaling mechanisms. In the bent form the integrin head group points inwards towards the cell surface and has low affinity for ligands [80]. During “inside-out signaling” an intracellular activator binds to the β-subunit, induces a conformational change leading to increased affinity for extracellular ligands [72]. This process is known to regulate cell adhesion, migration and invasion. During “outside-in signaling” a ligand binds to the integrin and can induce, because of multivalency, integrin clustering. Activation of a signal cascade leads to intracellular signals, which regulate cell polarity, survival and migration, changes in cytoskeleton and gene expression. The presence of unligated integrins can activate caspase-8, and as a consequence, induce apoptosis in a process known as IMD [78, 79].