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
  • 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: [email protected].
PMID: 30528319 DOI: 10.1016/j.clinre.2018.11.004
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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