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 CoCl2-treated ENO1-sh group were significantly elevated (P < 0.05). Transcriptomic sequencing indicated that CoCl2-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.

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

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;Department of Pathology,Tianjin Medical University,Tianjin 300070,China

癌症生物学与医学（英文版）

[1]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-.ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment)[J].癌症生物学与医学（英文版）,2022(11):1598-1616

PADC

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