Abstract
BackgroundIncreasing 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.MethodsWe 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.ResultsWe 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.ConclusionThe present study has demonstrated that RER1 enhances the progression of PC through promoting cell proliferation, migration and aggressiveness.
Highlights
With the developments in early detection, prevention and treatment of cancer, most cancers have showed a steadily declining incidence over the past several decades, with the exception of pancreatic cancer (PC)
Retention in endoplasmic reticulum 1 (RER1) is upregulated in PC tissues and is correlated with poor survival outcome To evaluate the role of RER1 in PC, we firstly examined the expression level of Rer1 in PC and adjacent normal tissues (Fig. 1a). 64% of primary PC tissues showed negative Rer1 expression, while 36% showed positive expression (n = 50)
We found that patients with higher RER1expression level showed worse overall survival rate and relapse free survival rate compared to those with low RER1 expression (Fig. 1h, i)
Summary
With the developments in early detection, prevention and treatment of cancer, most cancers have showed a steadily declining incidence over the past several decades, with the exception of pancreatic cancer (PC). One possible explanation for the high mortality rate of PC is the existence of cancer stem cells (CSCs) [5, 6]. These cells possess self-renewal ability and are capable of differentiation, tumorigenicity and metastasis [5, 7]. Most therapies target only tumor cells, allowing the escape of CSC population residing within the tumor causing the relapse of cancer resistant to chemotherapy and radiotherapy. Due to their important roles in cancer development and relapse, Chen et al Journal of Experimental & Clinical Cancer Research (2019) 38:15. It remains elusive whether RER1 is involved in the retention of disease-related proteins
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