Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors

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	Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors
	Cao, X; Tian, JH; Cheung, MY; Zhang, LY; Liu, ZM; Jiang, ZY; Zhang, ST; Xiao, K; Zhao, S; Wang, M; Ding, F; Li, SJ; Ma, LJ; Zhao, H; Sun, JM
	2024
发表期刊	CELL AND BIOSCIENCE
ISSN	2045-3701
卷号	14 期号:1
摘要	BackgroundZinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs).ResultsWe found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4-/- mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice.ConclusionsTaken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.
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/152453/14443
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Cao, X,Tian, JH,Cheung, MY,et al. Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors[J]. CELL AND BIOSCIENCE,2024,14(1).
APA	Cao, X.,Tian, JH.,Cheung, MY.,Zhang, LY.,Liu, ZM.,...&Sun, JM.(2024).Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors.CELL AND BIOSCIENCE,14(1).
MLA	Cao, X,et al."Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors".CELL AND BIOSCIENCE 14.1(2024).

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