RER1 enhances carcinogenesis and stemness of pancreatic cancer under hypoxic environment

Increasing incidence and mortality rates of pancreatic cancer (PC) highlight an urgent need for novel and efficient drugs. Retention in endoplasmic reticulum 1 (RER1) is an important retention factor in the endoplasmic reticulum (ER). However, it remains elusive whether RER1 is involved in the retention of disease-related proteins. We analyzed the expression level of RER1 in PC and adjacent tissues, and also employed Kaplan-Meier's analysis to identify the correlation between RER1 expression and overall survival rate. Cell proliferation, colony formation, tumor formation, scratch test, and transwell invasion assays were performed in RER1 knockdown cells and negative control cells. We hereby reported the important functions of RER1 in tumorigenesis and metastasis of PC, evidenced by inhibitory effects of RER1 knockdown on PC cell proliferation, migration and aggressiveness. Tumor formation was also significantly repressed in RER1 knockdown cells compared to control. Hypoxia-inducible factor (HIF)-1α was found to be an upstream regulator of RER1. Knockdown HIF-1α cells exhibited similar repressive impact on cell proliferation as RER1, and showed diminished migratory and invasive abilities under hypoxic condition. The present study has demonstrated that RER1 enhances the progression of PC through promoting cell proliferation, migration and aggressiveness.