Abstract 1087: The expression and activity of actin-regulating protein cofilin are associated with the cell cycle progression

Abstract

Cofilin is a member of actin depolymerizing factor (ADF)/cofilin family that can regulates actin dynamics for cancer growth and invasion/metastasis. Several lines of evidence have demonstrated that cofilin is associated with the cell cycle regulation, while the underlying mechanisms remain to be addressed. To better understand the involvement of cofilin in cell cycle progression, we dissected the cofilin expression and activity in different phases of the cell cycle. We synchronized human non-small lung A549 cancer cells in G1, S and G2/M phase by serum starvation, double thymidine blockage and nocodazole treatment, respectively. It was found that the expression of endogenous cofilin was weakest in G1 phase, while it was strongest in S phase and was modest in G2/M phase. This observation was further confirmed by detecting the down-regulation of highly expressed cofilin in S phase-synchronized cells entering mid-late S, G2/M and G1 phase of the cell cycle. Interestingly, it also showed that inactive form of cofilin (ser-3 phosphorylated) weakly expressed in S phase and gradually increased when cells progress through G2/M and G1 phases. These results suggest that cofilin expression and activity are coordinately regulated during the cell cycle progression. It is also consistent with our previous findings that enforced expression of cofilin results in G1 phase arrest but not S and G2/M phases. Moreover, the level of cofilin transcripts was not significantly altered in different phases of cell cycle. On the other hand, pretreatment of the proteasome inhibitor MG132 resulted in increase of cofilin in G1 phase, suggesting that the fluctuation of cofilin during cell cycle progression is associated with the protein stability. In addition, transduction of undegradable Y68F form of mutant cofilin potentially led to increase of the G1 percentage. Taken together, precisely regulation of cofilin expression and activity is important for cell cycle progression. Targeting on cofilin may provide alternative therapeutic strategy for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1087.