Metastasis is initiated by the migration of cancer cells away from the initial site of lesion to invade surrounding tissues. This process of cancer cell migration and invasion is regulated by changes in the actin cytoskeleton, the mechanical framework of a cell.  Many factors can affect actin dynamics and alter cell motility. In breast cancers, abberrant signaling through the epithelial growth factor (EGF) receptor is often associated with poor prognosis.  Although it is known that EGFR signaling contributes to cancer metastasis by promoting cell migration, the underlying molecular mechanism is not fully understood. We found that EGF-induced cell migration is dependent on the protein product of deleted in liver cancer 1 (DLC1), a gene that is deleted or mutated in a wide variety of cancers such as liver, lung, breast and prostate. The proposed research program is focused on understanding the signaling pathways and biochemical basis of DLC1 activation by a group of proteins called tensins. Tensin proteins are key regulators of the actin cytoskeleton, but their expressions are dynamically controlled by EGF. We expect our research to provide novel insights into the molecular basis of cancer metastasis and aid in efforts in exploiting the DLC1-tensin signaling axis for potential cancer intervention.