Abstract 1225: α-Catulin promotes tumor growth by preventing cellular senescence

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Cellular senescence is a proven tumor-suppressive strategy that forces transformed cancer cells to re-enter irreversible cell-cycle arrest. Triggering the senescence of tumor cells may contribute to successful cancer therapy. α-Catulin, an α-catenin-related protein, is reported to have tumorigenic potential because it regulates the NF-κB pathway, but little is known about its clinical relevance and the mechanism through which it regulates cancer progression. Here, we provide evidence that the expression of α-catulin is upregulated in most human cancer cells and clinical oral cancer tissues and positively correlated with tumor size (P = 0.001) and cancer stage (P = 0.004) of OSCC. α-Catulin knockdown in the OC2 and A549 cancer cell lines dramatically decreased cell proliferation and contributed to cellular senescence, and inhibited OC2 xenograft growth. Mechanistic dissection showed that α-catulin depletion strongly induced the DNA damage response (DDR) via a p53/p21-dependent pathway in A549 cells, but a p53/p21-independent pathway in OC2 cells carrying mutant p53. Global gene expression analysis revealed that α-catulin knockdown altered several crucial genes related to mitotic chromosome condensation, DDR, and DNA repair systems, which suggests that its depletion-induced cellular senescence might be caused by chromosome condensation failures, severe DNA damage, and impaired DNA repair ability. Our study provides evidence that α-catulin promotes tumor growth by preventing cellular senescence and suggests that downregulating α-catulin may be a promising therapeutic approach for cancer treatment. 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 1225. doi:10.1158/1538-7445.AM2011-1225