Mitochondrial STAT3 supports RasDependent oncogenic transformation

Daniel J Gough, Alicia Corlett, Karni Schlessinger, Joanna Wegrzyn, Andrew C Larner, David E Levy

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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.
Original languageEnglish
Pages (from-to)1713 - 1716
Number of pages4
JournalScience
Volume324
Issue number5935
DOIs
Publication statusPublished - 2009
Externally publishedYes

Cite this

Gough, D. J., Corlett, A., Schlessinger, K., Wegrzyn, J., Larner, A. C., & Levy, D. E. (2009). Mitochondrial STAT3 supports RasDependent oncogenic transformation. Science, 324(5935), 1713 - 1716. https://doi.org/10.1126/science.1171721