Comparing the Roles of the p110α and p110β Isoforms of PI3K in Signaling and Cancer

Abstract

Phosphatidylinositol-3-kinases (PI3K) are a family of enzymes thatact downstream of cell surface receptors leading to activation ofmultiple signaling pathways regulating cellular growth, proliferation,motility, and survival. To date, most research efforts have focusedon a group of PI3K-family enzymes termed class I, of which the moststudied member is PI3Kα. PI3Kα is an oncogene frequently mutatedin human cancer, as is the chief negative regulator of the pathway,the tumor suppressor PTEN. Recently, it has been suggested that tumorsdeficient for PTEN might depend on the function of another classI member, PI3Kβ, to sustain their transformed phenotype. Taken together,these findings provide a significant medical rationale to study thesignaling cascades regulated by PI3Kα and PI3Kβ particularly in thecontext of their role in the development and maintenance of humancancer. Here, we summarize the current understanding of the upstreamreceptor regulation of the two PI3K isoforms and their roles in canceras well as their functional requirements in downstream signalingcascades.