MUC1-C oncoprotein promotes STAT3 activation in an autoinductive regulatory loop.
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Date
2011Author
Ahmad, R
Rajabi, H
Kosugi, M
Joshi, MD
Alam, M
Vasir, B
Kawano, T
Kharbanda, S
Kufe, D
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Signal transducer and activator of transcription 3 (STAT3) is activated in human breast cancer and other malignancies. Mucin 1 (MUC1) is a heterodimeric cell surface glycoprotein that is overexpressed in human carcinomas and, like STAT3, promotes cell survival and induces transformation. We found that in breast cancer cells, the MUC1 carboxyl-terminal receptor subunit (MUC1-C) associates with the gp130-Janus-activated kinase 1 (JAK1)-STAT3 complex. The MUC1-C cytoplasmic domain interacted directly with JAK1 and STAT3, and MUC1-C was necessary for JAK1-mediated STAT3 activation. In turn, MUC1-C and activated STAT3 occupied the promoter of MUC1, and MUC1-C contributed to STAT3-mediated activation of MUC1 transcription. The MUC1-C inhibitor GO-201 blocked the MUC1-C interaction with STAT3, thereby decreasing MUC1-C and STAT3 occupancy on the MUC1 and STAT3 promoters and activation of STAT3 target genes, including MUC1 itself. These findings indicate that MUC1-C promotes STAT3 activation and that MUC1-C and STAT3 function in an autoinductive loop that may play a role in cancer cell survival.
URI
http://www.ncbi.nlm.nih.gov/pubmed/21325207http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/52692
Citation
Sci Signal. 2011 Feb 15;4(160):ra9. doi: 10.1126/scisignal.2001426.Publisher
University of Nairobi Faculty of medicine
Collections
- Faculty of Health Sciences (FHS) [10377]