During a search to identify resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV) target genes in the human erythroleukemic K562 cell line, we show here that the tensin gene and protein levels are remarkably induced by this dietary polyphenol. Tensin, a cell-matrix adhesion protein binding the integrins and cytoskeletal actin filaments also interacts with PI3-kinase and JNK signaling pathways. Tensin induction by RV is associated with increased K562 cell adhesion to fibronectin, cell spreading and actin polymerization. The same responses were observed in the tensin-deficient MCF7 human breast cancer cell line. In K562 and MCF7 cells treated by RV, tensin was found in punctate and intracytoplasmic areas. In MCF7 epithelial cells, induction of tensin is not exclusively associated with plasma membrane-bound vinculin, suggesting a dual localization of tensin in both focal and fibrillar adhesions. Pharmacological blockade of PI3-kinase and Rho GTPases/Rho-kinase resulted in selective depletion of focal adhesions, disorganization of tensin localization and disruption of stress fibers. RV increased cell motility and attachment to fibronectin in MCF7 cells submitted to mechanical laminar flow stress, and abrogated estrogen-induced MCF7 cancer cell invasion. Our data support the conclusion that induction of tensin by RV contributes to the chemopreventive and anti-invasive activity of this natural dietary compound in tensin-negative and -deficient leukemic cells or epithelioid cancers.