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Sci. Signal., 15 February 2011
Vol. 4, Issue 160, p. ra9
[DOI: 10.1126/scisignal.2001426]

RESEARCH ARTICLES

Editor's Summary

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.

Citation: R. Ahmad, H. Rajabi, M. Kosugi, M. D. Joshi, M. Alam, B. Vasir, T. Kawano, S. Kharbanda, D. Kufe, MUC1-C Oncoprotein Promotes STAT3 Activation in an Autoinductive Regulatory Loop. Sci. Signal. 4, ra9 (2011).

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MUC1-C Oncoprotein Activates ERK->C/EBP{beta} Signaling and Induction of Aldehyde Dehydrogenase 1A1 in Breast Cancer Cells.
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Oncogenic MUC1-C Promotes Tamoxifen Resistance in Human Breast Cancer.
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The MUC1-C Oncoprotein Binds to the BH3 Domain of the Pro-apoptotic BAX Protein and Blocks BAX Function.
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MUC1-C Oncoprotein Induces TCF7L2 Transcription Factor Activation and Promotes Cyclin D1 Expression in Human Breast Cancer Cells.
H. Rajabi, R. Ahmad, C. Jin, M. Kosugi, M. Alam, M. D. Joshi, and D. Kufe (2012)
J. Biol. Chem. 287, 10703-10713
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Mucin 1 C-Terminal Subunit Oncoprotein Is a Target for Small-Molecule Inhibitors.
Y. Zhou, H. Rajabi, and D. Kufe (2011)
Mol. Pharmacol. 79, 886-893
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