ENO1 Expression and Erk Phosphorylation in PDAC and Their Effects on Tumor Cell Apoptosis in a Hypoxic Microenvironment

Overview

Journal Cancer Biol Med

Specialty Oncology

Date 2022 Dec 8

PMID 36476328

Authors

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

Affiliations

Soon will be listed here.

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 CoCl-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated and . Hypoxia- and ENO1-induced gene expression was analyzed by transcriptomic sequencing.

Results: The prognosis of PDAC with high ENO1 expression was poor ( < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases ( < 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-treated ENO1-sh group were significantly elevated ( < 0.05). Transcriptomic sequencing indicated that CoCl-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis ( < 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.

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