Fig. 4.

Advances of the STAT3 signaling pathways involving breast cancer metastasis. Classical IL-6/JAK/STAT3 pathways activate the transcription of MMP2, MMP9, Twist, Snail, Slug and vimentin to promote breast cancer metastasis, which can be suppressed by MEST and activated by GRAMD1B. Wwox can inhibit the binding of IL-6 and IL-6R/gp130. IL-11 and KLF-11 can also activate STAT3 to promote breast cancer metastasis by binding to their receptors. ARHGAP24, MUC1-C, NPRA and OSM-mediated SMAD3 function to upregulate the phosphorylation of STAT3. Estrogen related receptor alpha (ERR-α) can be transcriptionally activated by STAT3 and promote breast cancer metastasis. Phosphorylated STAT3 induces the activation of VASP to inhibit the metastasis of breast cancer, whereas PIM1 induced by phosphorylated STAT3 may have the opposite effect. The combination of phosphorylated STAT3 and RhoU inhibits breast cancer metastasis. Additionally, TFEB can activate the phosphorylation of STAT3 and AKT to promote breast cancer metastasis