Mechanisms of PTEN loss in cancer: It's all about diversity

Semin Cancer Biol. 2019 Dec:59:66-79. doi: 10.1016/j.semcancer.2019.02.001. Epub 2019 Feb 7.

Abstract

PTEN is a phosphatase which metabolises PIP3, the lipid product of PI 3-Kinase, directly opposing the activation of the oncogenic PI3K/AKT/mTOR signalling network. Accordingly, loss of function of the PTEN tumour suppressor is one of the most common events observed in many types of cancer. Although the mechanisms by which PTEN function is disrupted are diverse, the most frequently observed events are deletion of a single gene copy of PTEN and gene silencing, usually observed in tumours with little or no PTEN protein detectable by immunohistochemistry. Accordingly, with the exceptions of glioblastoma and endometrial cancer, mutations of the PTEN coding sequence are uncommon (<10%) in most types of cancer. Here we review the data relating to PTEN loss in seven common tumour types and discuss mechanisms of PTEN regulation, some of which appear to contribute to reduced PTEN protein levels in cancers.

Keywords: Cancer; Mutation; PI 3-Kinase; PTEN; Tumour suppressor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Disease Susceptibility*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Loss of Function Mutation*
  • Mutation
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • PTEN Phosphohydrolase
  • PTEN protein, human