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Indexed by:期刊论文

Date of Publication:2018-01-01

Journal:Cell death & disease

Included Journals:PubMed、SCIE

Volume:9

Issue:5

Page Number:559

ISSN No.:2041-4889

Abstract:Breast cancer is a highly heterogeneous carcinoma in women worldwide, but the underlying mechanisms that account for breast cancer initiation and development have not been fully established. Mounting evidence indicates that Checkpoint suppressor 1 (CHES1) is tightly associated with tumorigenesis and prognosis in many types of cancer. However, the definitive function of CHES1 in breast cancer remains to be explored. Here we showed that CHES1 had a physical interaction with estrogen receptor-alpha (ERalpha) and repressed the transactivation of ERalpha in breast cancer cells. Mechanistically, the interaction between CHES1 and ERalpha enhanced the recruitment of nicotinamide adenine dinucleotide (NAD+) deacetylase Sirtuin 1 (SIRT1), and it further induced SIRT1-mediated ERalpha deacetylation and repression on the promoter-binding enrichment of ERalpha. In addition, we also found that the expression of CHES1 was repressed by estrogen-ERalpha signaling and the expression level of CHES1 was significantly downregulated in ERalpha-positive breast cancer. The detailed mechanism was that ERalpha may directly bind to CHES1 potential promoter via recognizing the conserved estrogen response element (ERE) motif in response to estrogen stimulation. Functionally, CHES1 inhibited ERalpha-mediated proliferation and tumorigenesis of breast cancer cells in vivo and in vitro. Totally, these results identified a negative cross-regulatory loop between ERalpha and CHES1 that was required for growth of breast cancer cells, it might uncover novel insight into molecular mechanism of CHES1 involved in breast cancer and provide new avenues for molecular-targeted therapy in hormone-regulated breast cancer.