DHHC protein family targets different subsets of glioma stem cells in specific niches | |
Chen, Xueran2,5; Hu, Lei1; Yang, Haoran1,5; Ma, Huihui3,4; Ye, Kaiqin2,5; Zhao, Chenggang1,5; Zhao, Zhiyang1,5; Dai, Haiming2,5; Wang, Hongzhi2,5; Fang, Zhiyou2,5 | |
刊名 | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2019-01-18 | |
卷号 | 38期号:无页码:16 |
关键词 | DHHC protein BMI1 Glioma stem cell Glioblastoma |
ISSN号 | 1756-9966 |
DOI | 10.1186/s13046-019-1033-2 |
英文摘要 | BackgroundGlioblastomas (GBM) comprise different subsets that exhibit marked heterogeneity and plasticity, leading to a lack of success of genomic profiling in guiding the development of precision medicine approaches against these tumors. Accordingly, there is an urgent need to investigate the regulatory mechanisms for different GBM subsets and identify novel biomarkers and therapeutic targets relevant in the context of GBM-specific niches. The DHHC family of proteins is associated tightly with the malignant development and progression of gliomas. However, the role of these proteins in the plasticity of GBM subsets remains unclear.MethodsThis study utilized human glioma proneural or mesenchymal stem cells as indicated. The effects of DHHC proteins on different GBM subsets were investigated through in vitro and in vivo assays (i.e., colony formation assay, flow cytometry assay, double immunofluorescence, western blot, and xenograft model). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to detect the protein complexes of ZDHHC18 and ZDHHC23 in various GBM subtypes, and explore the mechanism of DHHC proteins in targeting different subsets of GSCs in specific niches.ResultsZDHHC18 and ZDHHC23 could target the glioma stem cells of different GBM subsets in the context of their specific niches and regulate the cellular plasticity of these subtypes. Moreover, mechanistic investigations revealed that ZDHHC18 and ZDHHC23 competitively interact with a BMI1 E3 ligase, RNF144A, to regulate the polyubiquitination and accumulation of BMI1. These events contributed to the transition of glioma stem cells in GBM and cell survival under the stressful tumor microenvironment.ConclusionsOur work highlights the role of DHHC proteins in the plasticity of GBM subsets and reveals that BMI1 represents a potential therapeutic target for human gliomas. |
资助项目 | National Natural Science Foundation of China[81872066] ; National Natural Science Foundation of China[31501171] ; National Natural Science Foundation of China[31571433] ; National Natural Science Foundation of China[81773131] ; Anhui Provincial Natural Science Foundation[1608085MH180] ; Anhui Provincial Natural Science Foundation[1808085QH272] ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology[2018CXFX004] ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology[2017FXCX008] ; Youth Innovation Promotion Association of Chinese Academy of Sciences[2018487] |
WOS关键词 | SELF-RENEWAL ; ENDOTHELIAL-CELLS ; DNA-PKCS ; BMI1 ; GLIOBLASTOMA ; PROLIFERATION ; TUMORIGENICITY ; ACTIVATION ; EXPRESSION ; PHENOTYPE |
WOS研究方向 | Oncology |
语种 | 英语 |
出版者 | BMC |
WOS记录号 | WOS:000456238900001 |
资助机构 | National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; Anhui Provincial Natural Science Foundation ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; innovative program of Development Foundation of Hefei Center for Physical Science and Technology ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Youth Innovation Promotion Association of Chinese Academy of Sciences |
内容类型 | 期刊论文 |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/41593] ![]() |
专题 | 医学物理与技术中心 |
通讯作者 | Chen, Xueran; Fang, Zhiyou |
作者单位 | 1.Univ Sci & Technol China, 96 Jin Zhai Rd, Hefei 230031, Anhui, Peoples R China 2.Chinese Acad Sci, Hefei Canc Hosp, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China 3.Chinese Acad Sci, Hefei Inst Phys Sci, Key Lab Ion Beam Bioengn, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China 4.Anhui Med Univ, Affiliated Hosp 1, Dept Radiat Oncol, 218 Jixi Rd, Hefei 230031, Anhui, Peoples R China 5.Chinese Acad Sci, Hefei Inst Phys Sci, Ctr Med Phys & Technol, Anhui Prov Key Lab Med Phys & Technol, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Xueran,Hu, Lei,Yang, Haoran,et al. DHHC protein family targets different subsets of glioma stem cells in specific niches[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2019,38(无):16. |
APA | Chen, Xueran.,Hu, Lei.,Yang, Haoran.,Ma, Huihui.,Ye, Kaiqin.,...&Fang, Zhiyou.(2019).DHHC protein family targets different subsets of glioma stem cells in specific niches.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,38(无),16. |
MLA | Chen, Xueran,et al."DHHC protein family targets different subsets of glioma stem cells in specific niches".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 38.无(2019):16. |
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