STAT3 signaling in cancer. STAT3 signaling is activated by binding of various ligands to their cell surface receptors, leading to phosphorylation of STAT3. STAT3 also directly phosphorylated by Src and Abl, which are non-receptor tyrosine kinases. Phosphorylated STAT3 further homo-dimerized and translocated, to the nucleus. STAT3 regulate CyclinD1, c-Myc, Survivin, Bcl-XL, and Mcl1, which regulate cellular proliferation and survival. STAT3 up-regulates VEGF, bFGF, HGF, and HIF1α. Additionally, STAT3 also regulates MMP2, MMP9, Twist, and Vimentin, for invasion and migration. STAT3 activation also downregulates immune surveillance, by secretion of pro-inflammatory cytokines. Furthermore, maintaining cancer stem cell properties, STAT3 regulates Oct3/4, Nanog, CD133, and CD44.