Abstract B32: FOXOs support the metabolic requirements of normal and tumor cells by regulating IDH1 expression

FOXO transcription factors are considered bona fide tumor suppressors, however recent studies showed FOXOs are also required for tumor survival. Here we identify FOXOs as transcriptional regulators of IDH1. FOXOs regulate IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. In cancer cells carrying mutant IDH1, FOXOs likewise regulate mutant IDH1 expression and maintain the levels of the oncometabolite 2-hydroxyglutarate, which stimulates cancer cell proliferation likely by repressing differentiation. Combined, our data provide a new paradigm for the paradoxical role of FOXOs in both tumor suppression and promotion. Furthermore these data suggest a role for FOXOs in maintaining the de-differentiated state by regulating α-ketoglutarate and/or 2-hydroxyglutarate levels. Indeed, in models of differentiation (e.g. 3T3-L1 differentiation towards adipocytes) loss of FOXO, as well as loss of IDH1 expression repress differentiation and we are currently further exploring the molecular underpinnings.Note: This abstract was not presented at the conference.Citation Format: Paraskevi Charitou, Maria Rodriguez-Colman, Johan Gerrits, Nanda Verhoeven-Duif, Boudewijn Burgering. FOXOs support the metabolic requirements of normal and tumor cells by regulating IDH1 expression. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstr...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research