The Distinct Role Of CD73 In The Progression Of Pancreatic Cancer

Recent studies have shown that the non-enzymatic function of CD73 plays a key role in tumor progression,but this function of CD73 in pancreatic cancer cells has not been studied.Furthermore,little is known about the mechanism involved in CD73 regulation in tumors.Here,we found that CD73 expression was upregulated in pancreatic ductal adenocarcinoma(PDAC)and that its expression correlated with poor prognosis.CD73 knockdown inhibited cell growth and induced G1 phase arrest via the AKT/ERK/cyclin D signaling pathway.We also found that tumor necrosis factor receptor(TNFR)2 was involved in CD73-induced AKT and ERK signaling pathway activation in PDAC.Further,miR-30a-5p overexpression significantly increased the cytotoxic effect of gemcitabine in pancreatic cancer by directly targeting CD73 mRNA,suggesting that regulation of the miR-30a-5p/CD73 axis may play an important role in the development of gemcitabine resistance in pancreatic cancer.In summary,this regulatory network of CD73 appears to represent a new molecular mechanism underlying PDAC progression,and the mechanistic interaction between miR-30a-5p,CD73 and TNFR2 may provide new insights into therapeutic strategies for pancreatic cancer.