Abstract 2442: XIAP mediates cancer cell motility via RhoGDI-dependent regulation of cytoskeleton

Abstract

Abstract XIAP overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In the current study, we found that the deficiency of XIAP expression in human cancer cells by approach of either knockout or knockdown led to a marked reduction of β-Actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells in comparison to those in the parent wild type cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depended on its interaction with RhoGDI via XIAP's RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion, and offer further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic property. 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 2442. doi:10.1158/1538-7445.AM2011-2442