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We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during terminal differentiation of muscle cells, and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms. We further show that the M1-specific exon is actively repressed in cancer-cell lines\u2014although some M1 mRNA is expressed in cell lines derived from brain tumors\u2014and demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to this control. Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production. These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis.<\/jats:p>","DOI":"10.1073\/pnas.0914845107","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T04:53:28Z","timestamp":1263963208000},"page":"1894-1899","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":355,"title":["The alternative splicing repressors hnRNP A1\/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism"],"prefix":"10.1073","volume":"107","author":[{"given":"Cynthia V.","family":"Clower","sequence":"first","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Systems Biology, Harvard Medical School, Boston, MA 02115;"}]},{"given":"Deblina","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;"},{"name":"Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794;"}]},{"given":"Zhenxun","family":"Wang","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;"},{"name":"Watson School of Biological Sciences, Cold Spring Harbor, NY 11724; and"}]},{"given":"Lewis C.","family":"Cantley","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Systems Biology, Harvard Medical School, Boston, MA 02115;"}]},{"given":"Matthew G.","family":"Vander Heiden","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Systems Biology, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Adrian R.","family":"Krainer","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;"},{"name":"Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY 11794;"},{"name":"Watson School of Biological Sciences, Cold Spring Harbor, NY 11724; and"}]}],"member":"341","published-online":{"date-parts":[[2010,1,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06734"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.189"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1209"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0474923"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47947-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67091-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06667"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(98)00021-5"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-S1-S5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.13.1561"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.09.010"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.06.016"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2005.04.009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.00366.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M400182-MCP200"},{"key":"e_1_3_3_16_2","first-page":"223","article-title":"Antisense oligonucleotides as modulators of pre-mRNA splicing","volume":"133","author":"Sierakowska H","year":"2000","unstructured":"H Sierakowska, S Agrawal, R Kole, Antisense oligonucleotides as modulators of pre-mRNA splicing. 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