ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment
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 clinicopathologi...
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2022-11-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | https://www.cancerbiomed.org/content/19/11/1598 |
| _version_ | 1797980572028502016 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Huizhi Sun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T05:56:09Z |
| format | Article |
| id | doaj.art-353761a4dd4048a1b59236abeed331ee |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-04-11T05:56:09Z |
| publishDate | 2022-11-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-353761a4dd4048a1b59236abeed331ee2022-12-22T04:41:52ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412022-11-0119111598161610.20892/j.issn.2095-3941.2022.0451ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironmentHuizhi Sun0Jing Mo1Runfen Cheng2Fan Li3Yue Li4Yuhong Guo5Yanlei Li6Yanhui Zhang7Xiaoyu Bai8Yalei Wang9Xueyi Dong10Danfang Zhang11Jihui Hao12Tianjin 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, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaTianjin 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, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaTianjin 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, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaTianjin 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, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaTianjin 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, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Pathology, Tianjin Medical University, Tianjin 300070, ChinaTianjin 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, ChinaObjective: 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.https://www.cancerbiomed.org/content/19/11/1598pancreatic cancerhypoxiaeno1apoptosiserk phosphorylation |
| spellingShingle | 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 Cancer Biology & Medicine pancreatic cancer hypoxia eno1 apoptosis erk phosphorylation |
| title | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| title_full | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| title_fullStr | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| title_full_unstemmed | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| title_short | ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| title_sort | eno1 expression and erk phosphorylation in pdac and their effects on tumor cell apoptosis in a hypoxic microenvironment |
| topic | pancreatic cancer hypoxia eno1 apoptosis erk phosphorylation |
| url | https://www.cancerbiomed.org/content/19/11/1598 |
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