Systemic elevation of PTEN induces a tumor-suppressive metabolic state
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Isabel Garcia-Cao Min Sup Song Robin M Hobbs Gaelle Laurent Carlotta Giorgi Vincent CJ 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 PandolfiAbstract
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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Publisher website (DOI) 10.1016/j.cell.2012.02.030
Europe PubMed Central 22401813
Pubmed 22401813
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