PTEN and the PI3-kinase Pathway in Cancer

Overview

Journal Annu Rev Pathol

Publisher Annual Reviews

Specialty Pathology

Date 2008 Sep 5

PMID 18767981

Citations 594

Authors

Nader Chalhoub

Suzanne J Baker

Affiliations

Soon will be listed here.

Abstract

PI3-kinase and PTEN are major positive and negative regulators, respectively, of the PI3-kinase pathway, which regulates growth, survival, and proliferation. These key signaling components are two of the most frequently mutated proteins in human cancers, resulting in unregulated activation of PI3K signaling and providing irrefutable genetic evidence of the central role of this pathway in tumorigenesis. PTEN regulates PI3K signaling by dephosphorylating the lipid signaling intermediate PIP(3), but PTEN may have additional phosphatase-independent activities, as well as other functions in the nucleus. In this review, we highlight current work showing cancer-relevant complexities in the regulation of PTEN and PI3K activity, potential novel functions for PTEN, and feedback regulation within the pathway. The significance and complexity of PI3K signaling make it an important but challenging therapeutic target for cancer.

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