Research ArticleCancer

MUC1-C Oncoprotein Promotes STAT3 Activation in an Autoinductive Regulatory Loop

Sci. Signal.  15 Feb 2011:
Vol. 4, Issue 160, pp. ra9
DOI: 10.1126/scisignal.2001426

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Caught in a Loop

Mucin 1 (MUC1), a glycoprotein found at the apical surface of epithelial cells, is overexpressed in various carcinomas, including breast cancer; indeed, its overexpression can elicit cell transformation. The MUC1 carboxyl-terminal receptor subunit (MUC1-C) has been implicated in several signaling pathways, and here Ahmad et al. link it to signaling downstream of interleukin-6 (IL-6) and other inflammatory cytokines. They found that MUC1-C associated with components of the IL-6 receptor complex in breast cancer cells, in which it was required for JAK1-mediated phosphorylation of STAT3, and promoted STAT3 binding to and activation of target genes (including both MUC1 and STAT3). IL-6 stimulated a less prominent basal interaction between MUC1-C and STAT3 in nonmalignant breast epithelial cells. The authors thus propose that MUC1-C, by promoting activation of STAT3-dependent genes, may play a protective role in the inflammatory response of breast epithelial cells and that this response gets locked into an autoinductive loop in cancer cells, thereby promoting their resistance to cell death.