Secretome analysis of ionizing radiation‐induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration

Cellular senescence is a physiological program of irreversible growth arrest that is considered to play an important role in tumor suppression. Recent studies demonstrated that senescent cells secrete multiple growth regulatory proteins that could alter the behavior of neighboring cells. In this study, we investigated the effect of secretory proteins from ionizing radiation ( IR ) induced senescent tumor cells on normal and tumor cells. Conditioned medium ( CM ) from IR ‐induced senescent MCF 7 cells significantly increased cell proliferation, invasion, migration, and wound healing activity in MCF 7 cells and HUVEC s. Comparative proteomics analysis revealed 24 differentially secreted protein spots including Raf kinase inhibitor protein ( RKIP) , α‐ E nolase, AKAP 9, and MARK 4, and the findings were confirmed by W estern blot analysis of IR ‐induced senescent cancer cells. We found that RKIP was secreted via the classical pathway, and the transfection of small interfering RNA against RKIP suppressed CM ‐induced migration in MCF 7 cells. Treatment with recombinant human RKIP increased the migratory activity of MCF 7 cells. Taken together, our results demonstrate that the senescence‐associated secretory protein RKIP could be the principal target to prevent the potential effects of the secretome from IR ‐induced senescent tumor cells on neighboring cell migration.