| Title: | Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level |
| Authors: | Tanaka, Tsutomu Browse this author |
| Kutomi, Goro Browse this author |
| Kajiwara, Toshimitsu Browse this author |
| Kukita, Kazuharu Browse this author |
| Kochin, Vitaly Browse this author |
| Kanaseki, Takayuki Browse this author |
| Tsukahara, Tomohide Browse this author |
| Hirohashi, Yoshihiko Browse this author |
| Torigoe, Toshihiko Browse this author |
| Okamoto, Yoshiharu Browse this author |
| Hirata, Koichi Browse this author |
| Sato, Noriyuki Browse this author |
| Tamura, Yasuaki Browse this author →KAKEN DB |
| Keywords: | ERO1-alpha |
| VEGF |
| disulfide bond |
| triple-negative breast cancer |
| disulfide oxidase |
| angiogenesis |
| Issue Date: | 25-May-2016 |
| Publisher: | Nature Publishing Group |
| Journal Title: | British journal of cancer |
| Volume: | 114 |
| Issue: | 11 |
| Start Page: | 1227 |
| End Page: | 1234 |
| Publisher DOI: | 10.1038/bjc.2016.105 |
| Abstract: | 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. |
| Rights: | https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/65680 |
| Appears in Collections: | 産学・地域協働推進機構 (Institute for the Promotion of Business-Regional Collaboration) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
