2. Academic Validation
  3. EAG1 enhances hepatocellular carcinoma proliferation by modulating SKP2 and metastasis through pseudopod formation

EAG1 enhances hepatocellular carcinoma proliferation by modulating SKP2 and metastasis through pseudopod formation

  • Oncogene. 2021 Jan;40(1):163-176. doi: 10.1038/s41388-020-01522-6.
Jun Chen  # 1 2 3 4 5,  Zefeng Xuan  # 1 2 3 4 6,  Wenfeng Song 1 2 3 4,  Weili Han 5,  Hao Chen 1 2 3 4 5,  Yehui Du 7,  Haiyang Xie 1 2 3 4,  Yongchao Zhao 2 8,  Shusen Zheng 9 10 11 12,  Penghong Song 13 14 15 16
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China.
  • 3 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, China.
  • 4 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang Province, China.
  • 5 Department of Lung Transplantation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Division of Breast Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 7 Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 8 Institute of Translational Medicine, Zhejiang University School of Medicine, 310029, Hangzhou, China.
  • 9 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. shusenzheng@zju.edu.cn.
  • 10 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China. shusenzheng@zju.edu.cn.
  • 11 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, China. shusenzheng@zju.edu.cn.
  • 12 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang Province, China. shusenzheng@zju.edu.cn.
  • 13 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. songpenghong@zju.edu.cn.
  • 14 NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China. songpenghong@zju.edu.cn.
  • 15 Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, China. songpenghong@zju.edu.cn.
  • 16 Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, 310003, Zhejiang Province, China. songpenghong@zju.edu.cn.
  • # Contributed equally.
PMID: 33097858 DOI: 10.1038/s41388-020-01522-6
Abstract

Ether-à-go-go-1 (EAG1), one of the potassium channels, is involved in various physiological processes and plays an important role in the tumorigenesis of many kinds of Cancer. EAG1 is highly expressed in hepatocarcinoma cells and is closely related to clinical prognosis, but the molecular mechanism remains elusive. In this study, we verified that EAG1 promotes the proliferation of hepatocellular carcinoma (HCC) both in vitro and in vivo. It promotes cell cycle progression by inhibiting the ubiquitination of SKP2. In addition, EAG1 promotes the migration and invasion of HCC by promoting cell pseudopod formation. Furthermore, in a high-pressure plasmid-injected mouse liver orthotopic carcinoma model, astemizole, an EAG family blocker, can significantly inhibit the formation of liver Cancer. Meanwhile, liver-specific EAG1 knockout mice show resistance to hepatocarcinogenesis. This research demonstrated that EAG1 plays an important role in the progression of HCC, and could be a potential therapeutic target for HCC.

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