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ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST complex to chromatin

Author:
Li, Lifang  Liu, Xinhua  He, Lin  Yang, Jianguo  Pei, Fei  Li, Wanjin  Liu, Shumeng  Chen, Zhe  Xie, Guojia  Xu, Bosen  Ting, Xia  Zhang, Zihan  Jin, Tong  Liu, Xujun  Zhang, Wenting  Yuan, Shuai  Yang, Ziran  Wu, Chongyang  Zhang, Yu  Yang, Xiaohan  Yi, Xia  Liang, Jing  Shang, Yongfeng  Sun, Luyang  


Journal:
NATURE COMMUNICATIONS


Issue Date:
2017


Abstract(summary):

EGFR is required for animal development, and dysregulation of EGFR is critically implicated in malignant transformation. However, the molecular mechanism underlying the regulation of EGFR expression remains poorly explored. Here we report that the zinc-finger protein ZNF516 is a transcription repressor. ZNF516 is physically associated with the CtBP/LSD1/CoREST complex and transcriptionally represses a cohort of genes including EGFR that are critically involved in cell proliferation and motility. We demonstrate that the ZNF516-CtBP/LSD1/CoREST complex inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo. Significantly, low expression of ZNF516 is positively associated with advanced pathological staging and poor survival of breast carcinomas. Our data indicate that ZNF516 is a transcription repressor and a potential suppressor of EGFR, adding to the understanding of EGFR-related breast carcinogenesis and supporting the pursuit of ZNF516 as a potential therapeutic target for breast cancer.


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