Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State
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Vander Heiden_Systemic elevation.pdf
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Author(s)
Garcia-Cao, Isabel
Song, Min Sup
Hobbs, Robin M.
Laurent, Gaelle
Giorgi, Carlotta
de Boer, Vincent C. J.
Anastasiou, Dimitrios
Ito, Keisuke
Sasaki, Atsuo T.
Rameh, Lucia
Date Issued
March 2012
Journal
Cell
Publisher
Elsevier B.V.
Citation
Garcia-Cao, Isabel, 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. "Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State." Cell, 149.1 (2012): 49-62.© 2012 Elsevier Inc.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.cell.2012.02.030
