1. Academic Validation
  2. Targeting Mcl-1 inhibits survival and self-renewal of hepatocellular cancer stem-like cells

Targeting Mcl-1 inhibits survival and self-renewal of hepatocellular cancer stem-like cells

  • Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):292-300. doi: 10.1016/j.clinre.2018.11.004.
Huapeng Zhang 1 Gongquan Li 1 Guanghui Chen 1 Yi Zhang 2 Jie Pan 1 Hongwei Tang 1 Jie Li 1 Wenzhi Guo 1 Shuijun Zhang 3
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, PR China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, PR China.
  • 2 Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.
  • 3 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China; Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, Henan, PR China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, Henan, PR China. Electronic address: zhangshuijun@hotmail.com.
Abstract

Myeloid cell leukemia-1 (Mcl-1) is highly expressed in tumor tissues and cells of hepatocellular carcinoma (HCC), yet the role of Mcl-1 in Cancer stem-like cells (CSLCs) remains largely unclear. Herein, we showed that knockdown of Mcl-1 significantly inhibited HCC cells to form spheres under ultra-low attachment condition in serum-free medium, and also attenuated clone formation. Inhibition of Mcl-1 by specific inhibitors S63845 or A-1210477 hindered secondary sphere formation, triggered Apoptosis signaling and reduced the level of stem cell transcription factor Nanog, Sox2 and KLF4 in HCC spheroids cells. This study suggests that Mcl-1 is an essential factor for the survival and self-renewal of HCC CSLCs.

Keywords

Cancer stem-like cells; Hepatocellular carcinoma; Mcl-1; Mcl-1 inhibitor.

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