ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment  

作　　者：Huizhi Sun Jing Mo Runfen Cheng Fan Li Yue Li Yuhong Guo Yanlei Li Yanhui Zhang Xiaoyu Bai Yalei Wang Xueyi Dong Danfang Zhang Jihui Hao 

机构地区：[1]Tianjin Medical University Cancer Institute&Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China [2]Department of Pathology,Tianjin Medical University,Tianjin300070,China

出　　处：《Cancer Biology & Medicine》2022年第11期1598-1616,共19页癌症生物学与医学（英文版）

基　　金：supported by grants from the National Natural Science Key Foundation of China(Grant No.82030092).

摘　　要：Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remains unclear.Methods: The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl2-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated in vitro and in vivo. Hypoxia-and ENO1-induced gene expression was analyzed by transcriptomic sequencing.Results: The prognosis of PDAC with high ENO1 expression was poor(P < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases(P < 0.05). Hypoxia increased ENO1 expression in PDAC and promoted its migration and invasion. Apoptotic cells and the apoptosis marker caspase-3 in the CoCl_(2)-treated ENO1-sh group were significantly elevated(P < 0.05). Transcriptomic sequencing indicated that CoCl_(2)-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis(P < 0.05). Consistent results were also observed in a PDAC-bearing mouse hindlimb ischemia model.Conclusions: Hypoxia-induced ENO1 expression promotes ERK phosphorylation and inhibits apoptosis, thus leading to PDAC survival and invasion. These results suggest that ENO1 is a potential therapeutic target for PDAC.

关 键 词：Pancreatic cancer HYPOXIA ENOL APOPTOSIS Erk phosphorylation 

分 类 号：R735.9[医药卫生—肿瘤]