Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE
Summary: Glioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Hypoxia induces release of high-mobility group box 1 (HMGB1) from tumor cells, promoting the development of tumor. Here, we report that HMGB1 is overexpressed in...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222011440 |
| _version_ | 1811321375686656000 |
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| author | Cuifang Ye Huan Li Yachao Li Yang Zhang Guohao Liu Hailong Mi Honglian Li Qungen Xiao Li Niu Xingjiang Yu |
| author_facet | Cuifang Ye Huan Li Yachao Li Yang Zhang Guohao Liu Hailong Mi Honglian Li Qungen Xiao Li Niu Xingjiang Yu |
| author_sort | Cuifang Ye |
| collection | DOAJ |
| description | Summary: Glioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Hypoxia induces release of high-mobility group box 1 (HMGB1) from tumor cells, promoting the development of tumor. Here, we report that HMGB1 is overexpressed in human GBM specimens. Hypoxia promotes the expression and secretion of HMGB1 in GSCs. Furthermore, silencing HMGB1 results in the loss of stem cell markers and a reduction in self-renewal ability of GSCs. Additionally, HMGB1 knockdown inhibits the activation of RAGE-dependent ERK1/2 signaling pathway and arrests the cell cycle in GSCs. Consistently, FPS-ZM1, an inhibitor of RAGE, downregulates HMGB1 expression and the phosphorylation of ERK1/2, leading to a reduction in the proliferation of GSCs. In xenograft mice of GBM, HMGB1 knockdown inhibits tumor growth and promotes mouse survival. Collectively, these findings uncover a vital function for HMGB1 in regulating GSC self-renewal potential and tumorigenicity. |
| first_indexed | 2024-04-13T13:16:38Z |
| format | Article |
| id | doaj.art-cd8cbc0aa2f84355b2eceee8f11724a6 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T13:16:38Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-cd8cbc0aa2f84355b2eceee8f11724a62022-12-22T02:45:27ZengElsevieriScience2589-00422022-09-01259104872Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGECuifang Ye0Huan Li1Yachao Li2Yang Zhang3Guohao Liu4Hailong Mi5Honglian Li6Qungen Xiao7Li Niu8Xingjiang Yu9Department of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. ChinaDepartment of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. ChinaDepartment of Histology and Embryology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China; Corresponding authorSummary: Glioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Hypoxia induces release of high-mobility group box 1 (HMGB1) from tumor cells, promoting the development of tumor. Here, we report that HMGB1 is overexpressed in human GBM specimens. Hypoxia promotes the expression and secretion of HMGB1 in GSCs. Furthermore, silencing HMGB1 results in the loss of stem cell markers and a reduction in self-renewal ability of GSCs. Additionally, HMGB1 knockdown inhibits the activation of RAGE-dependent ERK1/2 signaling pathway and arrests the cell cycle in GSCs. Consistently, FPS-ZM1, an inhibitor of RAGE, downregulates HMGB1 expression and the phosphorylation of ERK1/2, leading to a reduction in the proliferation of GSCs. In xenograft mice of GBM, HMGB1 knockdown inhibits tumor growth and promotes mouse survival. Collectively, these findings uncover a vital function for HMGB1 in regulating GSC self-renewal potential and tumorigenicity.http://www.sciencedirect.com/science/article/pii/S2589004222011440Biological sciencesCancerCell biologyMicroenvironmentMolecular biology |
| spellingShingle | Cuifang Ye Huan Li Yachao Li Yang Zhang Guohao Liu Hailong Mi Honglian Li Qungen Xiao Li Niu Xingjiang Yu Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE iScience Biological sciences Cancer Cell biology Microenvironment Molecular biology |
| title | Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE |
| title_full | Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE |
| title_fullStr | Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE |
| title_full_unstemmed | Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE |
| title_short | Hypoxia-induced HMGB1 promotes glioma stem cells self-renewal and tumorigenicity via RAGE |
| title_sort | hypoxia induced hmgb1 promotes glioma stem cells self renewal and tumorigenicity via rage |
| topic | Biological sciences Cancer Cell biology Microenvironment Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222011440 |
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