GSK3 beta palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis

doi:10.1038/s41389-022-00402-w

	GSK3 beta palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis
	Zhao, Chenggang 1,2,5,6,7; Yu, Huihan 1,2,5; Fan, Xiaoqing 1,2,4,5,6,7; Niu, Wanxiang 1,2,5,6,7; Fan, Junqi 1,2,5,6,7; Sun, Suling 1,2,5,6,7; Gong, Meiting 1,2,5; Zhao, Bing 3; Fang, Zhiyou 1,2,5,6,7; Chen, Xueran 1,2,5,6,7
刊名	ONCOGENESIS
	2022-05-23
卷号	11
ISSN号	2157-9024
DOI	10.1038/s41389-022-00402-w
通讯作者	Zhao, Bing(aydzhb@126.com) ; Fang, Zhiyou(z.fang@cmpt.ac.cn) ; Chen, Xueran(xueranchen@cmpt.ac.cn)
英文摘要	Glioblastoma stem cells (GSCs) are a highly tumorigenic cell subgroup of glioblastoma (GBM). Glycogen synthase kinase 3 beta (GSK3 beta) is considered a key hub for promoting malignant phenotypes in GBM. However, the functional relationships between GSK3 beta and GSCs in GBM are unclear. Here, we found that GSK3 beta was noted as a substrate for ZDHHC4-mediated palmitoylation at the Cys14 residue, which enhanced GBM temozolomide (TMZ) resistance and GSC self-renewal. Clinically, the expression level of ZDHHC4 was upregulated in GBM, which significantly correlated with tumor grade and poor prognosis. The above phenotypes were based on decreasing p-Ser9 and increasing p-Tyr216 by GSK3 beta palmitoylation, which further activated the enhancer of the zeste homolog 2 (EZH2)-STAT3 pathway. Notably, STAT3 silencing also inhibited ZDHHC4 expression. This study revealed that GSK3 beta palmitoylation mediated by ZDHHC4 improved the stemness of TMZ-resistant GBM by activating the EZH2-STAT3 signaling axis, providing a new theoretical basis for further understanding the mechanism of TMZ resistance and recurrence after treatment.
资助项目	National Natural Science Foundation of China[81972635] ; National Natural Science Foundation of China[82172663] ; National Natural Science Foundation of China[82104208] ; National Natural Science Foundation of China[81872066] ; National Natural Science Foundation of China[81773131] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2018487] ; Innovative Program of Development Foundation of Hefei Centre for Physical Science and Technology[2021HSC-CIP011] ; National Key R&D Program of China[2017YFA0503600]
WOS关键词	GLYCOGEN-SYNTHASE KINASE-3 ; PHOSPHORYLATION ; METHYLATION ; INHIBITION ; ERA
WOS研究方向	Oncology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000799260200001
资助机构	National Natural Science Foundation of China ; Youth Innovation Promotion Association of the Chinese Academy of Sciences ; Innovative Program of Development Foundation of Hefei Centre for Physical Science and Technology ; National Key R&D Program of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/130957]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhao, Bing; Fang, Zhiyou; Chen, Xueran
作者单位	1.Chinese Acad Sci, Anhui Prov Key Lab Med Phys & Technol, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China 2.Chinese Acad Sci, Inst Hlth & Med Technol, Hefei Inst Phys Sci, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China 3.Anhui Med Univ, Dept Neurosurg, Affiliated Hosp 2, 678 Fu Rong Rd, Hefei 230601, Anhui, Peoples R China 4.Univ Sci & Technol China USTC, Affiliated Hosp USTC 1, Dept Anesthesiol, Div Life Sci & Med, 17 Lu Jiang Rd, Hefei 230001, Anhui, Peoples R China 5.Univ Sci & Technol China, MOE Key Lab Membraneless Organelles & Cellular Dy, 96 Jin Zhai Rd, Hefei 230027, Anhui, Peoples R China 6.Chinese Acad Sci, Hefei Canc Hosp, Dept Lab Med, 350 Shushan Hu Rd, Hefei 230031, Anhui, Peoples R China 7.Univ Sci & Technol China, Sci Isl Branch, Grad Sch, 96 Jin Zhai Rd, Hefei 230026, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Chenggang,Yu, Huihan,Fan, Xiaoqing,et al. GSK3 beta palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis[J]. ONCOGENESIS,2022,11.
APA	Zhao, Chenggang.,Yu, Huihan.,Fan, Xiaoqing.,Niu, Wanxiang.,Fan, Junqi.,...&Chen, Xueran.(2022).GSK3 beta palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis.ONCOGENESIS,11.
MLA	Zhao, Chenggang,et al."GSK3 beta palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2-STAT3 axis".ONCOGENESIS 11(2022).