Abstract IA15: New insights on the role of tumor suppressor phosphatases

Abstract

Abstract Because of the critical tumor suppressive role PTEN, its multiple layers of regulation have been the subject of intense investigation. Through its ability to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) PTEN suppresses the activation of the PI3K pathway. Its loss in turn results in the aberrant hyper-activation of AKT-mTOR signaling. Deletion, silencing and mutation of the PTEN phosphatase represents one of the most frequent events in human tumorigenesis. Reductions in PTEN levels are also tremendously consequential, resulting in cancer susceptibility and overt tumorigenesis in a cell type specific manner. In keeping with this notion PTEN is also found mutated in the germ line of individuals affected by PTEN Hamartoma Syndromes, characterized by developmental defects and cancer susceptibility. INPP4b, on the other hand, is an inositol polyphosphate-4-phosphatase, type II, that dephosphorylates the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. In so doing, INPP4b, like PTEN, can oppose the activation of the PI3K-Akt pathway. The INPP4b gene has been recently found frequently deleted in human cancers. On this basis we started investigating its putative tumor suppressive role both in vitro and in vivo in mouse models. Novel data emerging from the analysis of the critical role of these phosphatases in human cancer and disease pathogenesis will be presented. Citation Format: Pier Paolo Pandolfi. New insights on the role of tumor suppressor phosphatases. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr IA15.