Abstract
Pten inactivation promotes cell survival in leukemia cells by activating glycolytic metabolism. We found that targeting ribosomal protein S6 kinase 1 (S6K1) in Pten-deficient cells suppressed glycolysis and induced apoptosis. S6K1 knockdown decreased expression of HIF-1α, and HIF-1α was sufficient to restore glycolysis and survival of cells lacking S6K1. In the Pten(fl/fl) Mx1-Cre(+) mouse model of leukemia, S6K1 deletion delayed the development of leukemia. Thus, S6K1 is a critical mediator of glycolytic metabolism, cell survival, and leukemogenesis in Pten-deficient cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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Cell Line, Tumor
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Disease Models, Animal
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Gene Knockdown Techniques
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Glycolysis*
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Leukemia / enzymology*
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Leukemia / genetics
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Mice
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Mice, Knockout
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Ribosomal Protein S6 Kinases, 90-kDa / genetics
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
Substances
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1, alpha Subunit
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Neoplasm Proteins
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Ribosomal Protein S6 Kinases, 90-kDa
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Rps6ka1 protein, mouse
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PTEN Phosphohydrolase
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Pten protein, mouse