ERO1 promotes the proliferation and inhibits apoptosis of colorectal cancer cells by regulating the PI3K/AKT pathway

Endoplasmic reticulum oxidoreductin 1 alpha (ERO1 alpha) 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 ERO1 alpha 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 ERO1 alpha and analyze the clinical significance. ERO1 alpha was stably knocked-down in RKO and HT29 CRC cells to investigate its function and mechanism in vitro and in vivo. We found that ERO1 alpha was remarkably upregulated in CRC tissues and high ERO1 alpha expression is associated with N stage and poor prognosis of CRC patients. ERO1 alpha 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 ERO1 alpha knockdown in CRC cells. In vivo tumorigenicity assay also confirmed that ERO1 alpha knockdown suppressed tumor growth. Taken together, our findings demonstrated ERO1 alpha promotes the proliferation and inhibits apoptosis of CRC cells by regulating the PI3K/AKT pathway. High expression of ERO1 alpha is associated with poor prognosis in CRC patients, and ERO1 alpha could be a potential therapeutic target for CRC.