Activated PI3K Signaling as an Endogenous Inducer of p53 in Human Cancer

Abstract

Complex pathways exist in mammalian cells to regulate the expression and activity of oncogenes and tumor suppressor genes. Defining these regulatory pathways is an important step towards being able to interfere with tumorigenesis. Here we discuss our recent study indicating that activation of the phosphoinositide 3-kinase (PI3K) signaling pathway through inactivating mutations in PTEN or activating mutations in PIK3CA causes functional activation of p53 signaling in human cells. Our data suggest that activation of p53 is a fail-safe mechanism triggered by loss of PTEN or oncogenic activation of PI3K, and furthermore, that these events provide selective pressure to mutate p53.