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Cancer-associated oxidoreductase ERO1-? drives the production of VEGF via oxidative protein folding and regulating the mRNA level.
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ABSTRACT: Background
Endoplasmic reticulum disulfide oxidase 1-? (ERO1-?) 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-? is present in high levels in various types of tumours, and that ERO1-? is a novel factor of poor prognosis. However, how ERO1-? affects a tumour in vivo and why patients who have a tumour with a high expression level of ERO1-? have a poor prognosis are still unknown. Therefore, to clarify the mechanism, we investigated the effect of ERO1-? on a tumour from the point of view of angiogenesis.Methods
The effect of ERO1-? 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-?- overexpression or with ERO1-? knockdown was measured. The role of ERO1-? on VEGF expression was investigated. In triple-negative breast cancer cases, the relationship between expression of ERO1-? and angiogenesis was analysed.Results
We found that the expression of ERO1-? promoted tumour growth in a mouse study and angiogenesis. The effects of ERO1-? 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-? related to the number of the blood vessel. Furthermore, we found that ERO1-? was a poor prognosis factor in triple-negative breast cancer.Conclusions
Our study has established a novel link between expression of ERO1-? and secretion of VEGF, providing new evidence for the effectiveness of ERO1-?-targeted therapy in patients with ERO1-?-expressed cancer.
SUBMITTER: Tanaka T
PROVIDER: S-EPMC4891497 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level.
British journal of cancer 20160421 11
<h4>Background</h4>Endoplasmic reticulum disulfide oxidase 1-α (ERO1-α) 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-α is present in high levels in various types of tumours, and that ERO1-α is a novel factor of poor prognosis. However, how ERO1-α affects a tumour in vivo and why patients who have a tumour with a high expression level of ERO1-α have a poor p ...[more]