ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling
Metabolic reprogramming is a hallmark of cancer. The“Warburg effect”, also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC). Un...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003875 |
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| author | Aziguli Tulamaiti Shu-Yu Xiao Yan Yang Musitaba Mutailifu Xia-Qing Li Shi-Qi Yin Hong-Tai Ma Hong-Fei Yao Lin-Li Yao Li-Peng Hu Jun Li Shu-Heng Jiang Zhi-Gang Zhang Yan-Miao Huo Dong-Xue Li Xue-Li Zhang |
| author_facet | Aziguli Tulamaiti Shu-Yu Xiao Yan Yang Musitaba Mutailifu Xia-Qing Li Shi-Qi Yin Hong-Tai Ma Hong-Fei Yao Lin-Li Yao Li-Peng Hu Jun Li Shu-Heng Jiang Zhi-Gang Zhang Yan-Miao Huo Dong-Xue Li Xue-Li Zhang |
| author_sort | Aziguli Tulamaiti |
| collection | DOAJ |
| description | Metabolic reprogramming is a hallmark of cancer. The“Warburg effect”, also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC). Under hypoxic conditions, the “Warburg effect” occurs to meet the nutrient and energy demands of rapid genome replication, remodeling the tumor microenvironment (TME) and influencing tumor immunity. α-Enolase (ENO1) is a multifunctional protein, acting as a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid. ENO1 was found to be overexpressed in multiple types of cancers. Here, we investigated the role of ENO1 in modulating the PDAC microenvironment.Using bioinformatic analyses, we demonstrated that ENO1 was highly expressed in PDAC patients, which was related to a poor prognosis. In vitro, Eno1 knockdown resulted in reduced PDAC cell proliferation and colony formation, along with enhanced apoptosis in PDAC cells. In vivo, tumorigenesis was suppressed in mouse PDAC models by Eno1 knockdown. Flow cytometry analysis revealed that high expression of Eno1 altered the tumor immune microenvironment (TIME), particularly the impaired tumor infiltration and function of CD8+ T cells. Mechanistic studies revealed that ENO1 upregulated PD-L1 to prevent CD8+ T cells infiltration through the hypoxia-inducible factor (HIF)-1α signaling pathway, leading to PDAC progression.In conclusion, our findings indicate that ENO1 might serve as a potential biomarker for PDAC and a novel onco-immunotherapeutic target via its role in altering the TIME. |
| format | Article |
| id | doaj-art-bf1fb8de04494616a91fc959201f2fdf |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-bf1fb8de04494616a91fc959201f2fdf2025-01-22T05:41:31ZengElsevierTranslational Oncology1936-52332025-02-0152102261ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling Aziguli Tulamaiti0Shu-Yu Xiao1Yan Yang2Musitaba Mutailifu3Xia-Qing Li4Shi-Qi Yin5Hong-Tai Ma6Hong-Fei Yao7Lin-Li Yao8Li-Peng Hu9Jun Li10Shu-Heng Jiang11Zhi-Gang Zhang12Yan-Miao Huo13Dong-Xue Li14Xue-Li Zhang15State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Fengxian District Central Hospital, School of Medicine, Anhui University of Science and Technology, Shanghai, ChinaShanghai Fengxian District Central Hospital, School of Medicine, Anhui University of Science and Technology, Shanghai, ChinaShanghai Fengxian District Central Hospital, School of Medicine, Anhui University of Science and Technology, Shanghai, ChinaDepartment of Hepato-Biliary-Pancreatic Surgery, General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China; Corresponding author at: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China.State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding authors at: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding authors at: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.Metabolic reprogramming is a hallmark of cancer. The“Warburg effect”, also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC). Under hypoxic conditions, the “Warburg effect” occurs to meet the nutrient and energy demands of rapid genome replication, remodeling the tumor microenvironment (TME) and influencing tumor immunity. α-Enolase (ENO1) is a multifunctional protein, acting as a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid. ENO1 was found to be overexpressed in multiple types of cancers. Here, we investigated the role of ENO1 in modulating the PDAC microenvironment.Using bioinformatic analyses, we demonstrated that ENO1 was highly expressed in PDAC patients, which was related to a poor prognosis. In vitro, Eno1 knockdown resulted in reduced PDAC cell proliferation and colony formation, along with enhanced apoptosis in PDAC cells. In vivo, tumorigenesis was suppressed in mouse PDAC models by Eno1 knockdown. Flow cytometry analysis revealed that high expression of Eno1 altered the tumor immune microenvironment (TIME), particularly the impaired tumor infiltration and function of CD8+ T cells. Mechanistic studies revealed that ENO1 upregulated PD-L1 to prevent CD8+ T cells infiltration through the hypoxia-inducible factor (HIF)-1α signaling pathway, leading to PDAC progression.In conclusion, our findings indicate that ENO1 might serve as a potential biomarker for PDAC and a novel onco-immunotherapeutic target via its role in altering the TIME.http://www.sciencedirect.com/science/article/pii/S1936523324003875α-Enolase (ENO1)Tumor immune microenvironment (TIME)CD8+ T cellsPD-L1Hypoxia induced factor 1α (HIF-1α) |
| spellingShingle | Aziguli Tulamaiti Shu-Yu Xiao Yan Yang Musitaba Mutailifu Xia-Qing Li Shi-Qi Yin Hong-Tai Ma Hong-Fei Yao Lin-Li Yao Li-Peng Hu Jun Li Shu-Heng Jiang Zhi-Gang Zhang Yan-Miao Huo Dong-Xue Li Xue-Li Zhang ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling Translational Oncology α-Enolase (ENO1) Tumor immune microenvironment (TIME) CD8+ T cells PD-L1 Hypoxia induced factor 1α (HIF-1α) |
| title | ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling |
| title_full | ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling |
| title_fullStr | ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling |
| title_full_unstemmed | ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling |
| title_short | ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling |
| title_sort | eno1 promotes pdac progression by inhibiting cd8 t cell infiltration through upregulating pd l1 expression via hif 1α signaling |
| topic | α-Enolase (ENO1) Tumor immune microenvironment (TIME) CD8+ T cells PD-L1 Hypoxia induced factor 1α (HIF-1α) |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003875 |
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