Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression. Academic Article uri icon

Overview

abstract

  • Hyperactivation of the PI 3-kinase/AKT pathway is a driving force of many cancers. Here we identify the AKT-inactivating phosphatase PHLPP1 as a prostate tumor suppressor. We show that Phlpp1-loss causes neoplasia and, on partial Pten-loss, carcinoma in mouse prostate. This genetic setting initially triggers a growth suppressive response via p53 and the Phlpp2 ortholog, and reveals spontaneous Trp53 inactivation as a condition for full-blown disease. Surprisingly, the codeletion of PTEN and PHLPP1 in patient samples is highly restricted to metastatic disease and tightly correlated to deletion of TP53 and PHLPP2. These data establish a conceptual framework for progression of PTEN mutant prostate cancer to life-threatening disease.

publication date

  • August 16, 2011

Research

keywords

  • Mutation
  • Nuclear Proteins
  • PTEN Phosphohydrolase
  • Phosphoprotein Phosphatases
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC3176728

Scopus Document Identifier

  • 80051579092

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2011.07.013

PubMed ID

  • 21840483

Additional Document Info

volume

  • 20

issue

  • 2