TY - JOUR
T1 - Systemic elevation of PTEN induces a tumor-suppressive metabolic state
AU - Garcia-Cao, Isabel
AU - Song, Min Sup
AU - Hobbs, Robin M.
AU - Laurent, Gaelle
AU - Giorgi, Carlotta
AU - De Boer, Vincent C.J.
AU - Anastasiou, Dimitrios
AU - Ito, Keisuke
AU - Sasaki, Atsuo T.
AU - Rameh, Lucia
AU - Carracedo, Arkaitz
AU - Vander Heiden, Matthew G.
AU - Cantley, Lewis C.
AU - Pinton, Paolo
AU - Haigis, Marcia C.
AU - Pandolfi, Pier Paolo
PY - 2012/3/30
Y1 - 2012/3/30
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2012.02.030
DO - 10.1016/j.cell.2012.02.030
M3 - Article
C2 - 22401813
AN - SCOPUS:84859215796
SN - 0092-8674
VL - 149
SP - 49
EP - 62
JO - Cell
JF - Cell
IS - 1
ER -
