2. Academic Validation
  3. CHD1L augments autophagy-mediated migration of hepatocellular carcinoma through targeting ZKSCAN3

CHD1L augments autophagy-mediated migration of hepatocellular carcinoma through targeting ZKSCAN3

  • Cell Death Dis. 2021 Oct 15;12(10):950. doi: 10.1038/s41419-021-04254-x.
Xiaofeng Zhang 1 2,  Yinshan Bai 2 3,  Li Huang 2,  Shanshan Liu 2,  Yanxuan Mo 2,  Wei Cheng 2,  Guangliang Wang 2,  Zhiming Cao 1,  Xiaogang Chen 2,  Huiqing Cui 2,  Ling Qi 4,  Lei Ma 1,  Ming Liu 2,  Xin-Yuan Guan 5 6,  Ning-Fang Ma 7 8 9
Affiliations

Affiliations

  • 1 Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 2 Guangzhou Municipal and Guangdong ProvincialKey Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 3 School of Life Science and Engineering, Foshan University, Foshan, Guangdong, China.
  • 4 The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China.
  • 5 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 6 Department of Clinical Oncology, Center for Cancer Research, and State Key Laboratory for Liver Research, University of Hong Kong, Pok Fu Lam, Hong Kong.
  • 7 Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China. nfma@gzhmu.edu.cn.
  • 8 Guangzhou Municipal and Guangdong ProvincialKey Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China. nfma@gzhmu.edu.cn.
  • 9 Department of Histology and Embryology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China. nfma@gzhmu.edu.cn.
PMID: 34654797 DOI: 10.1038/s41419-021-04254-x
Abstract

Autophagy is an important biological process in normal cells. However, how it affects tumor progression still remains poorly understood. Herein, we demonstrated that the oncogenic protein Chromodomain-helicase-DNA-binding-protein 1-like gene (CHD1L) might promote HCC cells migration and metastasis through Autophagy. CHD1L could bind to the promotor region of Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3), a pivotal Autophagy suppressor, and inhibit its transcription. We established inducible CHD1L conditional knockout cell line (CHD1L-iKO cell) and found that the deletion of CHD1L significantly increased ZKSCAN3 expression both at mRNA and protein level. Deletion of CHD1L impaired the autophagic flux and migration of HCC cells, while specifically inhibiting ZKSCAN3 blocked these effects. Further exploration demonstrated that the enhanced tumor cell migration and metastasis induced by CHD1L was mediated through ZKSCAN3-induced autophagic degradation of Paxillin. In summary, we have characterized a previously unknown function of CHD1L in regulating tumor migration via ZKSCAN3-mediated Autophagy in HCC. Further inhibition of CHD1L and its downstream Autophagy signaling might shed new light on Cancer therapeutics.

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