Background:The tenascin-C-derived peptide TNIIIA2 is capable of activating ␤1-integrins. Results: TNIIIA2 greatly enhanced cell survival and PDGF-dependent proliferation through potentiated and sustained activation of integrin ␣5␤1, resulting in continuous proliferation even after reaching confluency. Conclusion: TNIIIA2-induced integrin ␣5␤1 activation causes deregulated cell growth. Significance: These results offer a new insight into the physiological/pathological role of tenascin-C in tissues where it is highly expressed.