Mitochondrial STAT3 supports RasDependent oncogenic transformation Journal Article
| Authors: | Gough, D. J.; Corlett, A.; Schlessinger, K.; Wegrzyn, J.; Larner, A. C.; Levy, D. E. |
| Article Title: | Mitochondrial STAT3 supports RasDependent oncogenic transformation |
| Abstract: | Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; genetics; mutation; nonhuman; mutant protein; protein function; cell proliferation; animal cell; mouse; animal; metabolism; animals; mice; cell survival; stat3 protein; signaling; cell line; animal model; mitochondrial membrane potential; pathology; cell line, tumor; phosphorylation; mice, inbred balb c; cell transformation, neoplastic; regulatory mechanism; bagg albino mouse; neoplastic stem cells; cell transformation; cancer cell; tumor cell line; cancer stem cell; protein transport; neoplasms, experimental; cytoplasm; stat3 transcription factor; ras protein; cell nucleus; experimental neoplasm; ras proteins; mutant proteins; genes, ras; mitochondria; cell metabolism; stat3 protein, human; mitochondrion; oxidation; glycolysis; oxidative phosphorylation; oncogene ras; membrane potential, mitochondrial |
| Journal Title: | Science |
| Volume: | 324 |
| Issue: | 5935 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2009-01-01 |
| Start Page: | 1713 |
| End Page: | 1716 |
| Language: | English |
| DOI: | 10.1126/science.1171721 |
| PUBMED: | 19556508 |
| PROVIDER: | scopus |
| PMCID: | PMC2840701 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 28" - "Export Date: 30 November 2010" - "CODEN: SCIEA" - "Source: Scopus" |
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