ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells
Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to t...
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| 格式: | 文件 |
| 语言: | English |
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Elsevier
2023-12-01
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| 丛编: | Acta Pharmaceutica Sinica B |
| 主题: | |
| 在线阅读: | http://www.sciencedirect.com/science/article/pii/S2211383523003581 |
| _version_ | 1827636296559886336 |
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| author | Mingjin Wang Weida Wang Shen You Zhenyan Hou Ming Ji Nina Xue Tingting Du Xiaoguang Chen Jing Jin |
| author_facet | Mingjin Wang Weida Wang Shen You Zhenyan Hou Ming Ji Nina Xue Tingting Du Xiaoguang Chen Jing Jin |
| author_sort | Mingjin Wang |
| collection | DOAJ |
| description | Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C–X–C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME. |
| first_indexed | 2024-03-09T15:41:03Z |
| format | Article |
| id | doaj.art-9c9c350f6b104275ab8c89c759bad447 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-09T15:41:03Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-9c9c350f6b104275ab8c89c759bad4472023-11-25T04:47:46ZengElsevierActa Pharmaceutica Sinica B2211-38352023-12-01131247334747ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cellsMingjin Wang0Weida Wang1Shen You2Zhenyan Hou3Ming Ji4Nina Xue5Tingting Du6Xiaoguang Chen7Jing Jin8Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaCorresponding authors. Tel./fax: +86 10 63165207.; Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaCorresponding authors. Tel./fax: +86 10 63165207.; Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaGlioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C–X–C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.http://www.sciencedirect.com/science/article/pii/S2211383523003581GlioblastomaMyeloid cellsMyeloid-derived suppressor cellsAcetyl-CoA acetyltransferase 1CXCL1Tumor microenvironment |
| spellingShingle | Mingjin Wang Weida Wang Shen You Zhenyan Hou Ming Ji Nina Xue Tingting Du Xiaoguang Chen Jing Jin ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells Acta Pharmaceutica Sinica B Glioblastoma Myeloid cells Myeloid-derived suppressor cells Acetyl-CoA acetyltransferase 1 CXCL1 Tumor microenvironment |
| title | ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells |
| title_full | ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells |
| title_fullStr | ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells |
| title_full_unstemmed | ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells |
| title_short | ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells |
| title_sort | acat1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid derived suppressor cells |
| topic | Glioblastoma Myeloid cells Myeloid-derived suppressor cells Acetyl-CoA acetyltransferase 1 CXCL1 Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523003581 |
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