STAT3 Pathway

STAT3 Is a Potent Oncogenic Signaling Pathway1,2

STAT3 is a transcription factor that, when overactivated, becomes an oncogenic signaling hub that promotes tumor progression through multiple effects including suppressing antitumor immunity, driving inflammation, and maintaining the undifferentiated state of cancer stem cells.1,2

STAT3 Activation Occurs Within Tumor Cells and the Tumor Microenvironment3,4

STAT3 signaling increases the expression of proinflammatory cytokines such as interleukin 6 (IL-6). These cytokines bind to surface receptors on cells within the tumor, resulting in an inflammatory positive feedback loop.2,3

Activated STAT3, which is phosphorylated, can be found in some tumors not only in tumor cells but also in cells of the tumor microenvironment, including stromal cells and some types of immune cells.4

STAT3=signal transducer and activator of transcription 3.

References

  1. Hajimoradi M, Mohammad Hassan Z, Ebrahimi M, et al. STAT3 is overactivated in gastric cancer stem-like cells. Cell J. 2016;17(4):617-628.
  2. Yuan J, Zhang F, Niu R. Multiple regulation pathways and pivotal biological functions of STAT3 in cancer. Sci Rep. 2015;5:17663. doi:10.1038/srep17663.
  3. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798-809.
  4. Chang A-Y, Hsu E, Patel J, et al. Evaluation of tumor cell–tumor microenvironment component interactions as potential predictors of patient response to napabucasin [manuscript under review]. Mol Cancer Res. 2019.