Non-redundant roles of the phosphoinositide phosphatases PTEN and PIPP in PI3K/AKT signaling in breast cancer

Abstract

Phosphoinositide 3-kinase (PI3K) signaling is hyperactivated in ~70% of breast cancers via mutations in oncogenes including PIK3CA or inactivation/depletion of phosphoinositide (PI)-phosphatases. Generation of PI(3,4,5)P3 by PI3K activates many downstream effectors, including AKT, that induce cellular proliferation in breast cancer. In this context PI(3,4,5)P3 is tightly regulated by PI-phosphatases, including the tumor suppressor PTEN and inositol polyphosphate 5-phosphatases such as PIPP/INPP5J. PTEN and PIPP dephosphorylate PI(3,4,5)P3 to form different lipid products, thereby individually regulating AKT activation. PI3K/AKT signaling is complex and the functional interplay between these ..