Abstract 1174: ASPP2: Tumor suppression through the control of polarity and proliferation

Abstract Cell polarity and proliferation are processes that play key roles in development. Loss of cell polarity and increased cellular proliferation are hallmarks of human cancer. The identification of molecules that are involved in the control of these processes is, therefore, important for our better understanding of tumor development and progression. p53 was recently found to be important in controlling the mammary epithelial stem cell pool. We have recently shown that ASPP2, a regulator of p53 and binding partner of many other proteins including YAP, is an important player in the regulation of cell polarity due to its ability to bind and regulate Par-3. Interestingly, ASPP2 is also able to directly regulate cell proliferation by affecting the activity of cyclin D1, by inhibiting the nuclear localisation of SUMO-modified cyclin D1. As ASPP2 is a haploinsufficient tumor suppressor, these findings identify ASPP2 as a unique regulator of cell polarity: able to influence cell polarity on the one hand and the cell cycle machinery on the other. ASPP2's interactions with p53, YAP and others, along with its potential role in controlling cell migration and EMT will be discussed. References Samuels-Lev Y, O'Connor DJ, Bergamaschi et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001 Oct;8(4):781-94. Vives V, Su J, Zhong S, Ratnayaka I, Slee E, Goldin R, Lu X. ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth. Genes Dev. 2006 May 15;20(10):1262-7. Sottocornola R, Royer C, Vives V et al. ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev Cell. 2010 Jul 20;19(1):126-37. Epub 2010 Jul 8. Wang XD, Lapi E, Sullivan A, Ratnayaka I, Goldin R, Hay R, Lu X. SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescence. Cell Death Differ. 2011 Feb;18(2):304-14. Epub 2010 Aug 27. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1174. doi:1538-7445.AM2012-1174