More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer.

IL-11, a member of the IL-6 family of cytokines, exerts pleiotropic activities by stimulating hemopoiesis and thrombopoiesis, regulating macrophage differentiation, and conferring mucosal protection in the intestine. These effects are mediated by a multimeric complex comprising the ligand-binding IL-11Rα and the ubiquitously expressed gp130R β-subunit, which together, trigger intracellular signaling and engagement of Stat3. In turn, activated Stat3 promotes cell survival and proliferation as well as immune responses associated with inflammatory diseases and tumor progression. IL-6 and IL-11 compete for interaction with gp130, resulting in tissue-specific functions depending on the expression patterns of their respective α-subunit receptors. Although traditionally, IL-6 has been associated with aberrant Stat3 activation and associated pathologies, here, we discuss newly emerging roles for IL-11 in linking inflammation to cancer progression. We propose that in light of the recurrence of persistent STAT3 activation and elevated IL-11 expression in inflammation-associated gastrointestinal cancers in humans, inhibition of Stat3 or pharmacologically, more amenable upstream molecules such as IL-11 may represent novel, therapeutic targets.