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Original Article | Open Access

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

Huizhi Sun1, Jing Mo2, Runfen Cheng1, Fan Li2, Yue Li2, Yuhong Guo1, Yanlei Li2, Yanhui Zhang1, Xiaoyu Bai2, Yalei Wang1, Xueyi Dong2, Danfang Zhang2 ( ), Jihui Hao1 ( )
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
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Abstract

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.

Keywords

hypoxiaPancreatic cancerapoptosisENO1Erk phosphorylation

Electronic Supplementary Material

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cbm-19-11-1598_ESM.pdf (2.4 MB)

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Cancer Biology & Medicine
Volume 19 Issue 11,
November 2022
Pages 1598-1616
DOI: 10.20892/j.issn.2095-3941.2022.0451
Cite this article:
Sun H, Mo J, Cheng R, et al. ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment. Cancer Biology & Medicine, 2022, 19(11): 1598-1616. https://doi.org/10.20892/j.issn.2095-3941.2022.0451

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Received: 28 July 2022
Accepted: 16 September 2022
Published: 05 December 2022
©2022 Cancer Biology & Medicine.

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