An intracellular signal pathway that regulates cancer cell adhesion in response to extracellular forces

Increasing evidence suggests that tumor cells can regulate their own adhesion via intracellular signals that modulate integrin binding affinity. Although the full pathway has not yet been elucidated, the effects of pressure seem likely to require cytoskeletal mechanosensing, Src, phosphati-dylinositol 3-kinase, focal adhesion kinase, and Akt-1 activation. Ultimately, activated focal adhesion kinase accumulates at the membrane in association with beta(1)-integrin heterodimers and may modulate integrin binding affinity. This pathway may be a promising target for manipulation to inhibit metastatic cancer cell adhesion.