Inflammation and cancer: IL-6 and STAT3 complete the link

Abstract

There is growing evidence that tumors are sustained and promoted by inflammatory signals from the surrounding microenvironment. Two papers by Grivennikov et al. and Bollrath et al. in this issue of Cancer Cell demonstrate the importance of the interleukin-6 family of proinflammatory cytokines and their downstream effector STAT3 in colitis-associated colon cancer.

Figure 1. Autocrine IL-6 Mediates gp130/JAK/STAT3 Signaling and Promotes Tumorigenesis

(A) IL-6 produced by inflammatory and stromal cells within the tumor microenvironment binds to gp80/gp130, leading to Janus kinase (JAK) activation and phosphorylation of STAT3, which regulates expression of genes mediating proliferation and preventing apoptosis. (B) Activated STAT3 (indicated by brown immunostaining) is found in tumor cells and inflammatory cells particularly on the invasive edge of tumors. (A breast carcinoma example is shown.)