IL-6/gp130/STAT3 signaling axis in cancer and the presence of in-frame gp130 somatic deletions in inflammatory hepatocellular tumors.

ABSTRACT

Evaluation of Rebouissou S, Amessou M, Couchy G et al. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature 457, 200-204 (2009). Recently, in-frame somatic deletions activating gp130, the receptor of IL-6, have been identified in inflammatory hepatocellular adenomas. This is a novel class of mutation in a receptor that is central to the IL-6/gp130/STAT3 pathway, which is relevant in a variety of cancers. STAT3 is a cancer transcriptional node activating several prosurvival and proliferation genes. The activation of IL-6/gp130 also promotes the activation of the RAS and PI3K pathways. Intriguingly, the overexpression of IL-6 and STAT3 has been observed in lung adenocarcinomas, including those with EGF-receptor mutations. Further clinical research should be performed on the IL-6/gp130/STAT3 signaling axis, since it constitutes an autocrine and paracrine amplification loop in several tumors, including those with RAS mutations.