2. Academic Validation
  3. NDRG1 facilitates self-renewal of liver cancer stem cells by preventing EpCAM ubiquitination

NDRG1 facilitates self-renewal of liver cancer stem cells by preventing EpCAM ubiquitination

  • Br J Cancer. 2023 May 10. doi: 10.1038/s41416-023-02278-y.
Qian Cheng # 1 2,  Shanglei Ning # 3,  Lei Zhu 4,  Changlu Zhang 4,  Shaodong Jiang 4,  Yajing Hao 5,  Jiye Zhu 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Beijing Key Laboratory of HCC and Liver Cirrhosis, Peking University People's Hospital, 100044, Beijing, China. chengqian@bjmu.edu.cn.
  • 2 Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. chengqian@bjmu.edu.cn.
  • 3 Department of General Surgery, Qilu Hospital of Shandong University, 250012, Shandong, China.
  • 4 Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 5 Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 6 Department of Hepatobiliary Surgery, Beijing Key Laboratory of HCC and Liver Cirrhosis, Peking University People's Hospital, 100044, Beijing, China. gandanwk@vip.sina.com.
  • # Contributed equally.
PMID: 37165202 DOI: 10.1038/s41416-023-02278-y
Abstract

Background: Portal vein tumour thrombus (PVTT) is the main pathway of HCC intrahepatic metastasis and is responsible for the poor prognosis of patients with HCC. However, the molecular mechanisms underlying PVTT vascular metastases have not been fully elucidated.

Methods: NDRG1 expression was assessed by immunohistochemistry and immunoblotting in clinical specimens obtained from curative surgery. The functional relevance of NDRG1 was evaluated using sphere formation and animal models of tumorigenicity and metastasis. The relationship between NDRG1 and EpCAM was explored using molecular biological techniques.

Results: NDRG1 protein was upregulated in HCC samples compared to non-tumorous tissues. Furthermore, NDRG1 expression was enhanced in the PVTT samples. Our functional study showed that NDRG1 was required for the self-renewal of tumour-initiating/Cancer Stem Cells (CSCs). In addition, NDRG1 knockdown inhibited the proliferation and migration of PVTT-1 cells in vitro and in vivo. NDRG1 was found to stabilise the functional tumour-initiating cell marker EpCAM through protein-protein interactions and inhibition of EpCAM ubiquitination.

Conclusion: Our findings suggest that NDRG1 enhances CSCs expansion, PVTT formation and growth capability through the regulation of EpCAM stability. NDRG1 may be a promising target for the treatment of patients with HCC and PVTT.

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