Systemic Elevation of PTEN Induces a Tumor-suppressive Metabolic State

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Mar 10

PMID 22401813

Citations 210

Authors

Isabel Garcia-Cao

Min Sup Song

Robin M Hobbs

Gaelle Laurent

Carlotta Giorgi

Vincent C J de Boer

Dimitrios Anastasiou

Keisuke Ito

Atsuo T Sasaki

Lucia Rameh

Arkaitz Carracedo

Matthew G Vander Heiden

Lewis C Cantley

Paolo Pinton

Marcia C Haigis

Pier Paolo Pandolfi

Affiliations

Soon will be listed here.

Abstract

Decremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial artificial chromosome (BAC)-mediated transgenesis. The "Super-PTEN" mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake and increased mitochondrial oxidative phosphorylation and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and -independent pathways and negatively impacting two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect.

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