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Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level

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タイトル: Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level
著者: Tanaka, Tsutomu 著作を一覧する
Kutomi, Goro 著作を一覧する
Kajiwara, Toshimitsu 著作を一覧する
Kukita, Kazuharu 著作を一覧する
Kochin, Vitaly 著作を一覧する
Kanaseki, Takayuki 著作を一覧する
Tsukahara, Tomohide 著作を一覧する
Hirohashi, Yoshihiko 著作を一覧する
Torigoe, Toshihiko 著作を一覧する
Okamoto, Yoshiharu 著作を一覧する
Hirata, Koichi 著作を一覧する
Sato, Noriyuki 著作を一覧する
Tamura, Yasuaki 著作を一覧する
キーワード: ERO1-alpha
VEGF
disulfide bond
triple-negative breast cancer
disulfide oxidase
angiogenesis
発行日: 2016年 5月25日
出版者: Nature Publishing Group
誌名: British journal of cancer
巻: 114
号: 11
開始ページ: 1227
終了ページ: 1234
出版社 DOI: 10.1038/bjc.2016.105
抄録: Background: Endoplasmic reticulum disulfide oxidase 1-alpha (ERO1-alpha) is an oxidase that exists in the endoplasmic reticulum and has a role in the formation of disulfide bonds of secreted proteins and cell-surface proteins. Recently, we reported that ERO1-alpha is present in high levels in various types of tumours, and that ERO1-alpha is a novel factor of poor prognosis. However, how ERO1-alpha affects a tumour in vivo and why patients who have a tumour with a high expression level of ERO1-alpha have a poor prognosis are still unknown. Therefore, to clarify the mechanism, we investigated the effect of ERO1-alpha on a tumour from the point of view of angiogenesis. Methods: The effect of ERO1-alpha on tumour growth and angiogenesis was analysed by using non-obese diabetic-severe combined immunodeficient mice. The production of vascular endothelial growth factor (VEGF) in MDA-MB-231 cells with ERO1-alpha-overexpression or with ERO1-alpha knockdown was measured. The role of ERO1-alpha on VEGF expression was investigated. In triple-negative breast cancer cases, the relationship between expression of ERO1-alpha and angiogenesis was analysed. Results: We found that the expression of ERO1-alpha promoted tumour growth in a mouse study and angiogenesis. The effects of ERO1-alpha on angiogenesis were mediated via oxidative protein folding of VEGF and enhancement of VEGF mRNA expression by using MDA-MB-231. In triple-negative breast cancer cases, the expression of ERO1-alpha related to the number of the blood vessel. Furthermore, we found that ERO1-alpha was a poor prognosis factor in triple-negative breast cancer. Conclusions: Our study has established a novel link between expression of ERO1-alpha and secretion of VEGF, providing new evidence for the effectiveness of ERO1-alpha-targeted therapy in patients with ERO1-alpha-expressed cancer.
資料タイプ: article
URI: http://hdl.handle.net/2115/65680
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 田村 保明

 

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