Systemic elevation of PTEN induces a tumor-suppressive metabolic state

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

Research output: Contribution to journalArticle

201 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)49-62
Number of pages14
JournalCell
Volume149
Issue number1
DOIs
StatePublished - Mar 30 2012
Externally publishedYes

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Tumors
Chromosomes
Glutamine
Phosphatidylinositol 3-Kinases
Metabolism
Neoplasms
Fats
Cells
Switches
Bacterial Artificial Chromosomes
Glucose
Gene Transfer Techniques
Oxidative Phosphorylation
Body Size
Cell Size
Energy Metabolism
Transgenic Mice
Adipose Tissue
Cell Count
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Garcia-Cao, I., Song, M. S., Hobbs, R. M., Laurent, G., Giorgi, C., De Boer, V. C. J., ... Pandolfi, P. P. (2012). Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell, 149(1), 49-62. https://doi.org/10.1016/j.cell.2012.02.030

Systemic elevation of PTEN induces a tumor-suppressive metabolic state. / 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; Carracedo, Arkaitz; Vander Heiden, Matthew G.; Cantley, Lewis C.; Pinton, Paolo; Haigis, Marcia C.; Pandolfi, Pier Paolo.

In: Cell, Vol. 149, No. 1, 30.03.2012, p. 49-62.

Research output: Contribution to journalArticle

Garcia-Cao, I, Song, MS, Hobbs, RM, Laurent, G, Giorgi, C, De Boer, VCJ, Anastasiou, D, Ito, K, Sasaki, AT, Rameh, L, Carracedo, A, Vander Heiden, MG, Cantley, LC, Pinton, P, Haigis, MC & Pandolfi, PP 2012, 'Systemic elevation of PTEN induces a tumor-suppressive metabolic state', Cell, vol. 149, no. 1, pp. 49-62. https://doi.org/10.1016/j.cell.2012.02.030
Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, De Boer VCJ et al. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012 Mar 30;149(1):49-62. https://doi.org/10.1016/j.cell.2012.02.030
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 ; Carracedo, Arkaitz ; Vander Heiden, Matthew G. ; Cantley, Lewis C. ; Pinton, Paolo ; Haigis, Marcia C. ; Pandolfi, Pier Paolo. / Systemic elevation of PTEN induces a tumor-suppressive metabolic state. In: Cell. 2012 ; Vol. 149, No. 1. pp. 49-62.
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