Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation

	Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation
	Liu, K; Jiang, LP; Shi, YL; Liu, BY; He, YM; Shen, QS; Jiang, XL; Nie, Z; Pu, J; Yang, CP; Chen, YB
	2022
发表期刊	CELL DEATH AND DIFFERENTIATION
ISSN	1350-9047
卷号	29 期号:9 页码:1834-1849
摘要	Gliomas are the most aggressive primary brain tumors. However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1 alpha under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. Directly blocking the GLT8D1/CD133 complex formation by CD133(N1 similar to 108) (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/beta-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/beta-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13283
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Liu, K,Jiang, LP,Shi, YL,et al. Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation[J]. CELL DEATH AND DIFFERENTIATION,2022,29(9):1834-1849.
APA	Liu, K.,Jiang, LP.,Shi, YL.,Liu, BY.,He, YM.,...&Chen, YB.(2022).Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation.CELL DEATH AND DIFFERENTIATION,29(9),1834-1849.
MLA	Liu, K,et al."Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation".CELL DEATH AND DIFFERENTIATION 29.9(2022):1834-1849.

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