title: Secretome analysis of ionizing radiation-induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration.
abstract: 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 MCF7 cells significantly increased cell proliferation, invasion, migration, and wound healing activity in MCF7 cells and HUVECs. Comparative proteomics analysis revealed 24 differentially secreted protein spots including Raf kinase inhibitor protein (RKIP), α-Enolase, AKAP9, and MARK4, and the findings were confirmed by Western 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 MCF7 cells. Treatment with recombinant human RKIP increased the migratory activity of MCF7 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.
authors: Divisions of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Na-Kyung
authors: NK
authors: Han
authors: Bong Cho
authors: BC
authors: Kim
authors: Hyung Chul
authors: HC
authors: Lee
authors: Yoon-Jin
authors: YJ
authors: Lee
authors: Myung-Jin
authors: MJ
authors: Park
authors: Sung-Gil
authors: SG
authors: Chi
authors: Young-Gyu
authors: YG
authors: Ko
authors: Jae-Seon
authors: JS
authors: Lee
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D002465:Cell Movement / Q000528:radiation effects*; D016922:Cellular Senescence / Q000528:radiation effects*; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D061986:MCF-7 Cells; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D034741:RNA, Small Interfering; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection
chemical_list: D017077:Culture Media, Conditioned; D049488:Phosphatidylethanolamine Binding Protein; D020543:Proteome; D034741:RNA, Small Interfering