Cellular senescence is an irreversible growth arrest mechanism that prevents indefinite proliferation of mammalian cells. Change of morphology is a common characteristic of senescent cells, while the underlying mechanism has not been completely addressed. In this study, we found that the flattened and enlarged cell shape in aged WI-38 fibroblast was accompanied by reduced actin cytoskeletal organization and up-regulated cofilin-1, a member of actin depolymerization factor family. Up-regulation of cofilin-1 was also detected in various tissues (lung, kidney, heart and liver) of one-year old BALB/c mice compared to that of 6-week old mice. Forced expression of cofilin-1 in early passaged cells accelerated senescence, while knockdown of cofilin-1 in late passaged cells inhibited senescence. Hydrogen peroxide mediated stress-induced premature senescence (SIPS) also induced cofilin-1 in human lung cancer cell lines, and this phenomenon was suppressed by knockdown of cofilin-1. Up-regulation of cofilin-1 in SIPS was independent of p53, while p27kip1 was essential for cofilin-1 induced senescence. Knockdown of p27kip1 in cells treated with hydrogen peroxide or in that with over-expressed cofilin alleviated senescence. Moreover, forced expression of cofilin-1 was sufficient to induce senescence in human lung cancer cells and repress the growth of xenograft tumor in NOD-SCID mice. Taken together, we found that cofilin-1 is able to mediate the cell senescence that is important for repressing the cancer development.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1243. doi:10.1158/1538-7445.AM2011-1243