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Posttranslational regulation of phosphatase and tensin homolog (PTEN) and its functional impact on cancer behaviors

Authors Xu WT, Yang Z, Zhou SF, Lu NH

Received 12 July 2014

Accepted for publication 4 August 2014

Published 6 October 2014 Volume 2014:8 Pages 1745—1751

DOI https://doi.org/10.2147/DDDT.S71061

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Professor Wei Duan

Wenting Xu,1 Zhen Yang,1 Shu-Feng Zhou,2 Nonghua Lu1

1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA


Abstract: The incidence of cancer is increasing worldwide, but the biochemical mechanisms for the occurrence of cancer is not fully understood, and there is no cure for advanced tumors. Defects of posttranslational modifications of proteins are linked to a number of important diseases, such as cancer. This review will update our knowledge on the critical role of posttranscriptional regulation of phosphatase and tensin homolog (PTEN) and its activities and the functional impact on cancer behaviors. PTEN is a tumor suppressor gene that occupies a key position in regulating cell growth, proliferation, apoptosis, mobility, signal transduction, and other crucial cellular processes. The activity and function of PTEN are regulated by coordinated epigenetic, transcriptional, posttranscriptional, and posttranslational modifications. In particular, PTEN is subject to phosphorylation, ubiquitylation, somoylation, acetylation, and active site oxidation. Posttranslational modifications of PTEN can dynamically change its activity and function. Deficiency in the posttranslational regulation of PTEN leads to abnormal cell proliferation, apoptosis, migration, and adhesion, which are associated with cancer initiation, progression, and metastasis. With increasing information on how PTEN is regulated by multiple mechanisms and networked proteins, its exact role in cancer initiation, growth, and metastasis will be revealed. PTEN and its functionally related proteins may represent useful targets for the discovery of new anticancer drugs, and gene therapy and the therapeutic potentials should be fully explored.

Keywords: phosphorylation, ubiquitination, acetylation, oxidation, PTEN

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