The STAT (signal transducer and activator of transcription) proteins are activated in response to receptor stimulation and act in the nucleus to regulate gene expression. Gough et al. found that STAT3 functioned in transformation of cells by the oncogene Ras. However, this activity was maintained in mutants of STAT that fail to activate transcription. Instead, the active STAT3 appeared to be associated with mitochondria. Furthermore, modified STAT3 targeted to the mitochondria promoted transformation by Ras, and mitochondrial function was disrupted in Ras-transformed cells lacking STAT3. Such transformation-specific effects of STAT3 could be a useful target in developing anticancer therapies.
D. J. Gough, A. Corlett, K. Schlessinger, J. Wegrzyn, A. C. Larner, D. E. Levy, Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324, 1713–1716 (2009). [Abstract] [Full Text]