2. Academic Validation
  3. Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

  • Cell Death Dis. 2021 Apr 14;12(4):397. doi: 10.1038/s41419-021-03686-9.
Yanli Bi 1 2 3,  Longyuan Gong 1 2 3,  Pengyuan Liu 3,  Xiufang Xiong 3 4,  Yongchao Zhao 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 5 Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yongchao@zju.edu.cn.
  • 6 Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yongchao@zju.edu.cn.
  • 7 Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. yongchao@zju.edu.cn.
  • 8 Cancer Center, Zhejiang University, Hangzhou, China. yongchao@zju.edu.cn.
PMID: 33854045 DOI: 10.1038/s41419-021-03686-9
Abstract

ErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast Cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of Autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for Autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/Akt/mTOR pathway to inhibit Autophagy.

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    99.91%, ERBB2/HER2 Inhibitor
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