Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency
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 t...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-02, Vol.108 (6), p.2361-2365 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Tandon, Preeti Gallo, Catherine A Khatri, Shikha Barger, Jennifer F Yepiskoposyan, Hasmik Plas, David R |
| description | 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 Ptenfl/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. |
| doi_str_mv | 10.1073/pnas.1013629108 |
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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 Ptenfl/fl Mx1-Cre⁺ mouse model of leukemia, S6K1 deletion delayed the development of leukemia. 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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 Ptenfl/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.</description><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological Sciences</subject><subject>Bone marrow cells</subject><subject>Cancer</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Cellular metabolism</subject><subject>Cultured cells</subject><subject>Disease Models, Animal</subject><subject>Gene expression</subject><subject>Gene expression regulation</subject><subject>Gene Knockdown Techniques</subject><subject>Glycolysis</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia - enzymology</subject><subject>Leukemia - genetics</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - genetics</subject><subject>Ribosomal Protein S6 Kinases, 90-kDa - metabolism</subject><subject>Rodents</subject><subject>Survival analysis</subject><subject>Viability</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ks2P1SAUxRujcd6Mrl2pZDa6qXP5KKUbEzPxK5lE4zhrQlt48myhA1TT_17qG9-MLtzAJfw4HO6hKJ5geIWhpmeTUzFXmHLSYBD3ig2GBpecNXC_2ACQuhSMsKPiOMYdADSVgIfFEcGEE0HrTfHzi76ebdCjdgkZH1CwrY9-VAOagk_aOnTJ0Xeb79EIo-TRqHurkkbbYen8sEQbkXI9UpOfkl9XQecxKddpZF0_d7pH7YI-J-1Qr43trHbd8qh4YNQQ9eOb-aS4evf26_mH8uLT-4_nby7KrhJ1Kjk3TPWCs7pSBjTDHJOGgTE9rlmuW6pMRZsGcEMbqCtRdUQYANxi1lNR0ZPi9V53mtvsvMvPDGqQU7CjCov0ysq_d5z9Jrf-h6RARY1JFnhxIxD89axjkqONnR4G5bSfoxQVJrmZnGby5X9JzLigVTa5ip7-g-78HFxuxKpHOWVshc72UBd8jEGbg2sMck1frunL2_TziWd3H3vg_8R9B1hP3soJySWhHGfg6R7YxeTDgWA4fyX4bfz5ft8oL9U22CivLkl2kANgQASjvwDpEMge</recordid><startdate>20110208</startdate><enddate>20110208</enddate><creator>Tandon, Preeti</creator><creator>Gallo, Catherine A</creator><creator>Khatri, Shikha</creator><creator>Barger, Jennifer F</creator><creator>Yepiskoposyan, Hasmik</creator><creator>Plas, David R</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110208</creationdate><title>Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency</title><author>Tandon, Preeti ; 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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 Ptenfl/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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>21262837</pmid><doi>10.1073/pnas.1013629108</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals Apoptosis Biological Sciences Bone marrow cells Cancer Cell growth Cell Line, Tumor Cell lines Cells Cellular metabolism Cultured cells Disease Models, Animal Gene expression Gene expression regulation Gene Knockdown Techniques Glycolysis Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Kinases Leukemia Leukemia - enzymology Leukemia - genetics Metabolism Mice Mice, Knockout Neoplasm Proteins - genetics Neoplasm Proteins - metabolism PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism Ribosomal Protein S6 Kinases, 90-kDa - genetics Ribosomal Protein S6 Kinases, 90-kDa - metabolism Rodents Survival analysis Viability |
| title | Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency |
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