Normal epithelial cells that lose the integrindependent anchorage to their extracellular matrix trigger anoikis,while metastatic tumor cells bypass anoikis pathway, which is one of the key events to achieve the metastasis. Physiological role of anoikis is also involved during embryonic development and tissue homeostasis, suggesting that anoikis must be strictly regulated at some level. Despite its importance, the molecular pathways involved in the regulation of anoikis and the proximal signals reporting loss of anchorage are poorly understood. Recent studies suggest an adaptor protein p66Shc, localizing at focal adhesions,mediates anoikis through activation of RhoA. However, expression of p66Shc is inadequate in metastatic cancer cells, failing to initiate anoikis and promoting tumor metastasis. Reexpression of proapoptotic protein p66Shc can restore the susceptibility to anoikis.Thus, p66Shc may be a potential target molecule for diagnosis of tumor metastasis and for tumor treatment.
