Hypoxia-inducible ERO1α promotes cancer progression through modulation of integrin-ß1 modification and signalling in HCT116 colorectal cancer cells.
Sci Rep
; 7(1): 9389, 2017 08 24.
Article
de En
| MEDLINE
| ID: mdl-28839225
ABSTRACT
Endoplasmic reticulum disulphide oxidase 1α (ERO1α) is an oxidase localized in the endoplasmic reticulum that plays a role in the formation of disulphide bonds of secreted and cell-surface proteins. We previously showed that ERO1α is overexpressed in various types of cancer and we further identified ERO1α expression as a novel factor related to poor prognosis in cancer. However, the biological functions of ERO1α in cancer remain unclear. Here, we investigated the cell biological roles of ERO1α in the human colon-cancer cell line HCT116. ERO1α knockout (KO) by using CRISPR/Cas9 resulted in decreased tumourigenicity in vivo and reduced cell proliferation only under hypoxia in vitro, which suggested that ERO1α promotes cancer progression specifically in a low-oxygen environment. Thus, we evaluated the function of ERO1α in cell proliferation under hypoxia, and found that under hypoxic conditions, ERO1α KO resulted in a contact-inhibited morphology and diminished motility of cells. We further showed that ERO1α KO induced a change in integrin-ß1 glycosylation and thus an attenuation of cell-surface integrin-ß1 expression, which resulted in the aforementioned phenotype. Our study has established a previously unrecognized link between ERO1α expression and integrin activation, and thus provides new evidence for the effectiveness of ERO1α-targeted therapy for colorectal carcinoma.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Oxidoreductases
/
Glycoprotéines membranaires
/
Transduction du signal
/
Antigènes CD29
/
Hypoxie
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Sci Rep
Année:
2017
Type de document:
Article
Pays d'affiliation:
Japon