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

Lifang Li, Xinhua Liu, Lin He, Jianguo Yang, Fei Pei, Wanjin Li, Shumeng Liu, Zhe Chen, Guojia Xie, Bosen Xu, Xia Ting, Zihan Zhang, Tong Jin, Xujun Liu, Wenting Zhang, Shuai Yuan, Ziran Yang, Chongyang Wu, Yu Zhang, Xiaohan Yang, Xia Yi, Jing Liang, Yongfeng Shang and Luyang Sun ()
Additional contact information
Lifang Li: Peking University Health Science Center
Xinhua Liu: Tianjin Medical University
Lin He: Peking University Health Science Center
Jianguo Yang: Peking University Health Science Center
Fei Pei: Peking University Health Science Center
Wanjin Li: Peking University Health Science Center
Shumeng Liu: Peking University Health Science Center
Zhe Chen: Peking University Health Science Center
Guojia Xie: Peking University Health Science Center
Bosen Xu: Peking University Health Science Center
Xia Ting: Peking University Health Science Center
Zihan Zhang: Peking University Health Science Center
Tong Jin: Peking University Health Science Center
Xujun Liu: Peking University Health Science Center
Wenting Zhang: Peking University Health Science Center
Shuai Yuan: Peking University Health Science Center
Ziran Yang: Peking University Health Science Center
Chongyang Wu: Peking University Health Science Center
Yu Zhang: Peking University Health Science Center
Xiaohan Yang: Peking University Health Science Center
Xia Yi: Peking University Health Science Center
Jing Liang: Peking University Health Science Center
Yongfeng Shang: Peking University Health Science Center
Luyang Sun: Peking University Health Science Center

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00702-5

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