Checkpoint suppressor 1 suppresses transcriptional activity of ERα and breast cancer cell proliferation via deacetylase SIRT1.

Cell Death & Disease
Zhaowei XuHuijian Wu

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-α (ERα) and repressed the transactivation of ERα in breast cancer cells. Mechanistically, the interaction between CHES1 and ERα enhanced the recruitment of nicotinamide adenine dinucleotide (NAD+) deacetylase Sirtuin 1 (SIRT1), and it further induced SIRT1-mediated ERα deacetylation and repression on the promoter-binding enrichment of ERα. In addition, we also found that the expression of CHES1 was repressed by estrogen-ERα signaling and the expression level of CHES1 was significantly downregulated in ERα-positive breast cancer. The detailed mechanism was that ERα may directly bind to CHES1 potential promoter via recognizing the conserved estrogen response element (ERE) motif in response to estrogen stimulation. Functionally, CHES1 inhibited ...Continue Reading

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Citations

Oct 16, 2018·Frontiers in Endocrinology·Sergio LiarteFrancisco José Nicolás
Jun 18, 2020·OncoTargets and Therapy·Jun ZhouTao Huang
Feb 23, 2020·International Journal of Laboratory Hematology·Jinjing ZhangYan Li
Nov 2, 2018·Cancers·Khaldoun RifaïDominique Bernard-Gallon
Jun 21, 2021·Biochimica Et Biophysica Acta. General Subjects·Liz M Garcia-Peterson, Xiaoling Li

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Methods Mentioned

BETA
acetylation
co-immunoprecipitation
CoIP
PCR
immunoprecipitation
ChIP
xenograft
electrophoresis
Flow Cytometry
reverse transcription-PCR

Software Mentioned

ImageJ

Related Concepts