フルテキストファイル
著者
Asai, Ryoma Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University
Tsuchiya, Hiroyuki Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University 研究者総覧 KAKEN
Amisaki, Masataka Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University / Faculty of Medicine, Division of Surgical Oncology, Department of Surgery, Tottori University KAKEN
Makimoto, Kazuki Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University
Takenaga, Ai Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University
Sakabe, Tomohiko Faculty of Medicine, Division of Organ Pathology, Department of Pathology, Tottori University 研究者総覧 KAKEN
Hoi, Shotaro Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University
Koyama, Shigemi Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University
Shiota, Goshi Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University 研究者総覧 KAKEN
キーワード
cancer stem cell
CD44
hepatocellular carcinoma
NOTCH3
oxidative stress
抄録
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several variant isoforms. CD44v is a major isoform expressed on CSCs of a variety of tumors and has been extensively studied. However, HCC tissues dominantly express CD44s, whose function in CSCs remains unclear. In the present study, we investigated the roles of CD44s in CSCs of HCC. Knock-out of the CD44 gene in HuH7 HCC cells on which only CD44s is expressed resulted in decreased spheroid formation and increased drug sensitivity. The expression of CSC marker genes, including CD133 and EpCAM, was significantly downregulated in the spheroids of CD44-deficient cells compared with those in the spheroids of HuH7 cells. In addition, CD44 deficiency impaired antioxidant capacity, concomitant with downregulation of glutathione peroxidase 1 (GPX1) and thioredoxin. Because GPX1 uses the reduced form of glutathione (GSH) to regenerate oxidized cellular components, GSH levels were significantly increased in the CD44-deficient cells. We also found that NOTCH3 and its target genes were downregulated in the spheroids of CD44-deficient cells. NOTCH3 expression in HCC tissues was significantly increased compared with that in adjacent nontumor liver tissues and was correlated with CD44 expression. These results suggest that CD44s is involved in maintenance of CSCs in a HCC cell line, possibly through the NOTCH3 signaling pathway.
出版者
WILEY
資料タイプ
学術雑誌論文
外部リンク
ISSN
20457634
掲載誌名
CANCER MEDICINE
最新掲載誌名
CANCER MEDICINE
8
2
開始ページ
773
終了ページ
782
発行日
2019-02
出版者DOI
著者版フラグ
出版社版
著作権表記
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
掲載情報
Asai Ryoma, Tsuchiya Hiroyuki, Amisaki Masataka, et al. CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line. CANCER MEDICINE. 2019. 8(2). 773-782. doi:10.1002/cam4.1968
部局名
医学部・医学系研究科・医学部附属病院
言語
英語
Web of Science Key ut
WOS:000459306700027