PT  - JOURNAL ARTICLE
AU  - Huizhi Sun
AU  - Jing Mo
AU  - Runfen Cheng
AU  - Fan Li
AU  - Yue Li
AU  - Yuhong Guo
AU  - Yanlei Li
AU  - Yanhui Zhang
AU  - Xiaoyu Bai
AU  - Yalei Wang
AU  - Xueyi Dong
AU  - Danfang Zhang
AU  - Jihui Hao
TI  - ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment
AID  - 10.20892/j.issn.2095-3941.2022.0451
DP  - 2022 Nov 15
TA  - Cancer Biology & Medicine
PG  - 1598--1616
VI  - 19
IP  - 11
4099  - http://www.cancerbiomed.org/content/19/11/1598.short
4100  - http://www.cancerbiomed.org/content/19/11/1598.full
SO  - Cancer Biology & Medicine2022 Nov 15; 19
AB  - 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.