ERO1α promotes the proliferation and inhibits apoptosis of colorectal cancer cells by regulating the PI3K/AKT pathway.

Endoplasmic reticulum oxidoreductin 1α (ERO1α) is an oxidase that exists in the endoplasmic reticulum and plays an important role in regulating oxidized protein folding and tumor malignant progression. However, the specific role and mechanism of ERO1α in the progression of colorectal cancer (CRC) have not yet been fully elucidated. In this study, 280 specimens of CRC tissues and adjacent noncancerous tissues were collected to detect the expression of ERO1α and analyze the clinical significance. ERO1α was stably knocked-down in RKO and HT29 CRC cells to investigate its function and mechanism in vitro and in vivo. We found that ERO1α was remarkably upregulated in CRC tissues and high ERO1α expression is associated with N stage and poor prognosis of CRC patients. ERO1α knockdown in CRC cells significantly inhibited the proliferation and induced apoptosis while inactivating the PI3K/AKT pathway. Rescue assays revealed that AKT activator 740Y-P could reverse the effects on proliferation and apoptosis of ERO1α knockdown in CRC cells. In vivo tumorigenicity assay also confirmed that ERO1α knockdown suppressed tumor growth. Taken together, our findings demonstrated ERO1α promotes the proliferation and inhibits apoptosis of CRC cells by regulating the PI3K/AKT pathway. High expression of ERO1α is associated with poor prognosis in CRC patients, and ERO1α could be a potential therapeutic target for CRC.