Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis

Yoshiharu Muto, Toshiro Moroishi, Kazuya Ichihara, Masaaki Nishiyama, Hideyuki Shimizu, Hidetoshi Eguchi, Kyoji Moriya, Kazuhiko Koike, Koshi Mimori, Masaki Mori, Yuta Katayama, Keiichi Nakayama

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.

元の言語英語
ページ(範囲)950-965
ページ数16
ジャーナルJournal of Experimental Medicine
216
発行部数4
DOI
出版物ステータス出版済み - 4 1 2019

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Carcinogenesis
Homeostasis
Iron
Iron Overload
Liver
Hepatocellular Carcinoma
Ligases
Ubiquitin
Carcinogens
Hepatocytes
Oxidative Stress
Viruses
Inflammation
Neoplasms

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. / Muto, Yoshiharu; Moroishi, Toshiro; Ichihara, Kazuya; Nishiyama, Masaaki; Shimizu, Hideyuki; Eguchi, Hidetoshi; Moriya, Kyoji; Koike, Kazuhiko; Mimori, Koshi; Mori, Masaki; Katayama, Yuta; Nakayama, Keiichi.

:: Journal of Experimental Medicine, 巻 216, 番号 4, 01.04.2019, p. 950-965.

研究成果: ジャーナルへの寄稿記事

Muto, Y, Moroishi, T, Ichihara, K, Nishiyama, M, Shimizu, H, Eguchi, H, Moriya, K, Koike, K, Mimori, K, Mori, M, Katayama, Y & Nakayama, K 2019, 'Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis' Journal of Experimental Medicine, 巻. 216, 番号 4, pp. 950-965. https://doi.org/10.1084/jem.20180900
Muto Y, Moroishi T, Ichihara K, Nishiyama M, Shimizu H, Eguchi H その他. Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. Journal of Experimental Medicine. 2019 4 1;216(4):950-965. https://doi.org/10.1084/jem.20180900
Muto, Yoshiharu ; Moroishi, Toshiro ; Ichihara, Kazuya ; Nishiyama, Masaaki ; Shimizu, Hideyuki ; Eguchi, Hidetoshi ; Moriya, Kyoji ; Koike, Kazuhiko ; Mimori, Koshi ; Mori, Masaki ; Katayama, Yuta ; Nakayama, Keiichi. / Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. :: Journal of Experimental Medicine. 2019 ; 巻 216, 番号 4. pp. 950-965.
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