دورية أكاديمية
MUC1-C activates EZH2 expression and function in human cancer cells
| العنوان: | MUC1-C activates EZH2 expression and function in human cancer cells |
|---|---|
| المؤلفون: | Rajabi, Hasan, Hiraki, Masayuki, Tagde, Ashujit, Alam, Maroof, Bouillez, Audrey, Christensen, Camilla L., Samur, Mehmet, Wong, Kwok-Kin, Kufe, Donald |
| المصدر: | Rajabi, Hasan, Masayuki Hiraki, Ashujit Tagde, Maroof Alam, Audrey Bouillez, Camilla L. Christensen, Mehmet Samur, Kwok-Kin Wong, and Donald Kufe. 2017. “MUC1-C activates EZH2 expression and function in human cancer cells.” Scientific Reports 7 (1): 7481. doi:10.1038/s41598-017-07850-0. http://dx.doi.org/10.1038/s41598-017-07850-0Test. |
| بيانات النشر: | Nature Publishing Group UK, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | HMS Scholarly Articles SPH Scholarly Articles |
| الوصف: | The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells. |
| نوع الوثيقة: | Journal Article |
| اللغة: | English |
| العلاقة: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547076/pdfTest/; Scientific Reports |
| DOI: | 10.1038/s41598-017-07850-0 |
| الوصول الحر: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:34375271Test |
| حقوق: | open URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAATest |
| رقم الانضمام: | edshld.1.34375271 |
| قاعدة البيانات: | Digital Access to Scholarship at Harvard (DASH) |
| DOI: | 10.1038/s41598-017-07850-0 |
|---|