Dataset Information

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

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.

SUBMITTER: Sun H

PROVIDER: S-EPMC9724225 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Sun Huizhi H Mo Jing J Cheng Runfen R Li Fan F Li Yue Y Guo Yuhong Y Li Yanlei Y Zhang Yanhui Y Bai Xiaoyu X Wang Yalei Y Dong Xueyi X Zhang Danfang D Hao Jihui J

Cancer biology & medicine 20221201 11

<h4>Objective</h4>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.<h4>Methods</h4>The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl<sub>2</sub>-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC ce ...[more]

PMID: 36476328

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Project description:The tumor microenvironment (TME) influences the occurrence and progression of tumors, and hypoxia is an important characteristic of the TME. The expression of programmed death 1 (PD1)/programmed death-ligand 1 (PDL1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), and other immune checkpoints in hypoxic malignant tumors is often significantly increased, and is associated with poor prognosis. The application of immune checkpoint inhibitors (ICIs) for treating lung cancer, urothelial carcinoma, and gynecological tumors has achieved encouraging efficacy; however, the rate of efficacy of ICI single-drug treatment is only about 20%. In the present review, we discuss the possible mechanisms by which the hypoxic TME regulates immune checkpoints. By activating hypoxia-inducible factor-1α (HIF-1α), regulating the adenosine (Ado)-A2aR pathway, regulating the glycolytic pathway, and driving epithelial-mesenchymal transition (EMT) and other biological pathways, hypoxia regulates the expression levels of CTLA4, PD1, PDL1, CD47, lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain 3 (TIM3), and other immune checkpoints, which interfere with the immune effector cell anti-tumor response and provide convenient conditions for tumors to escape immune surveillance. The combination of HIF-1α inhibitors, Ado-inhibiting tumor immune microenvironment regulatory drugs, and other drugs with ICIs has good efficacy in both preclinical studies and phase I-II clinical studies. Exploring the effects of TME hypoxia on the expression of immune checkpoints and the function of infiltrating immune cells has greatly clarified the relationship between the hypoxic TME and immune escape, which is of great significance for the development of new drugs and the search for predictive markers of the efficacy of immunotherapy for treating malignant tumors. In the future, combination therapy with hypoxia pathway inhibitors and ICIs may be an effective anti-tumor treatment strategy.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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