Focal adhesion kinase (FAK), as a key mediator of signaling induced by integrins, plays an instrumental role in many cellular functions, including cell survival and proliferation. Many studies have reported that FAK is a positive regulator of normal cell migration and cancer cell metastasis. However, emerging evidence shows that FAK--under certain oncogenic signaling, such as that initiated by activated Ras and some growth factor receptor kinases--negatively regulates cancer cell migration. Activated Ras may promote tumor cell migration by dephosphorylation of FAK at Y397 and facilitation of focal adhesion turnover at the leading edge of cells.