Fig. 1

The STAT3 signaling pathway in cancer cells. Under normal physiological conditions, STAT3 activation is strictly controlled by the endogenous inhibitors, including the protein inhibitor of activated STAT (PIAS), the suppressor of cytokine signaling (SOCS), and several protein tyrosine phosphatases (PTPs). Once the upstream cytokines (e.g., IL-6) or growth factors (e.g., EGF, FGF, and VEGF) bind to cell surface receptors, STAT3 is phosphorylated and activated by JAK or Src. The nonreceptor tyrosine kinases (e.g., Src and Abl) also phosphorylate STAT3. The phosphorylated STAT3 undergoes dimerization and translocates from cytoplasm into the nucleus. The activated STAT3 further binds to DNA and its coactivators (e.g., NCOA, APE, and CBP) and induces the transcription of its downstream target genes