Abstract 2254: FIP200 regulation by hypoxia in brain endothelial cells

Abstract

Abstract Angiogenesis is a prominent characteristic of glioblastoma tumors. Hypoxia occurs in glioblastoma tumors and is thought to promote angiogenesis largely through a HIF-dependent mechanism. The effect of hypoxia on survival proteins expressed by endothelial cells (ECs), such as focal adhesion kinase interacting protein of 200kDa (FIP200, also known as RB1CC1), has received little attention. We recently reported that the expression of FIP200 is increased in the angiogenic endothelial cells of glioblastoma tumors. FIP200 can promote cell survival through its promotion of autophagy, or by inhibiting Pyk2 activation and Pyk2-mediated apoptosis. We found that hypoxia upregulated FIP200 protein expression and that this upregulation of FIP200 was independent of the downregulation of ARNT, suggesting it was HIF-independent. We then examined the post-translational modification of FIP200 and whether it was differentially regulated in hypoxia. We found that FIP200 is degraded in the proteosome in normoxia, and that there may be alterations in the proteosomal degradation pathway in hypoxia that contribute, in part, to the elevated FIP200 protein level. Understanding the mechanism for the increased expression of FIP200 in hypoxia may provide future therapeutic targets for new anti-angiogenic therapy. 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 2254. doi:1538-7445.AM2012-2254