Figure 1.

IL-6/JAK/STAT3 signaling; A) Classical-signaling: IL-6 binds to mIL-6 R, and interplays with membrane gp 130; B) Trans-signaling: sIL-6R cleaved from macrophage membranes binds to IL-6 and then the complex interplays with membrane gp130; Then the complex IL-6 / IL-6R / gp130 triggers the activation of JAK, and meanwhile the suppressor of cytokine signalling (SOCS) acts on JAKs and stops phosphorylation of gp130, STATs and the JAKs themselves. STAT3 (an oncogenic transcriptional factor) is activated by JAKs, phosphorylated and formed dimers (pSTAT3-pSTAT3). The dimerised pSTAT3 complex moves to nucleus and pSTAT3 complex trigger transcription of STAT3 target genes (cyclin D1, VEGF, c-myc, etc) through interaction with DNA. Cancer promotion is initiated. The protein inhibitors of activated STATs (PIAS) can suppress the transcription of STAT3 target genes