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PMID: 18767981 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

PTEN and the PI3-kinase pathway in cancer.

Annual review of pathology ·Vol. 4 ·2009-00-00 ·Pages 127-50

Chalhoub N, Baker SJ

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.

MeSH Terms
Animals Antineoplastic Agents/pharmacology Cell Transformation, Neoplastic/genetics,metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genetic Therapy Humans Mice Models, Animal Mutation Neoplasms/enzymology,genetics,pathology,therapy PTEN Phosphohydrolase/genetics,metabolism Phosphatidylinositol 3-Kinases/genetics,metabolism Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors/pharmacology Signal Transduction/drug effects,genetics
Chemicals
Antineoplastic Agents Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors PTEN Phosphohydrolase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chalhoub Nader
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. [email protected]
Baker Suzanne J
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Article Info
Journal
Annual review of pathology
Abbr.
Annu Rev Pathol
ISSN
1553-4014
DOI
10.1146/annurev.pathol.4.110807.092311
Email
[email protected]
Published
2009-00-00
Pages
127-50
Language
English
Region
United States
NLM ID
101275111
PMCID
PMC2710138
Subset
IM
Grants
NCI NIH HHS · P01 CA096832 · United States
NCI NIH HHS · P01 CA096832-05 · United States
NCI NIH HHS · R01 CA135554 · United States
NCI NIH HHS · R01 CA135554-06A1 · United States
External Links
PubMed source DOI: 10.1146/annurev.pathol.4.110807.092311 PMC Full Text View journal details
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