TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms

	TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms
	Guo, L; Ke, H; Zhang, HL; Zou, L; Yang, Q; Lu, XM; Zhao, LM; Jiao, BW
	2022
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	13 期号:5
摘要	Alternative splicing (AS) is a promising clinical target for cancer treatment at the post-transcriptional level. We previously identified a unique AS profile in triple-negative breast cancer (TNBC), which is regulated by the splicing regulator TAR DNA-binding protein-43 (TDP43), thus indicating the crucial role of TDP43 in heterogeneous TNBC. Cluster of differentiation 44 (CD44), a widely recognized marker for breast cancer stem cells (BCSCs), is extensively spliced into CD44 variant AS isoforms (CD44v) during the development of breast cancer. At present, however, the regulatory mechanism of CD44v is not fully understood. In the current study, we found that loss of TDP43 inhibits BCSC stemness by reducing the abundance of CD44v. In addition, serine-arginine-rich splicing factor 3 (SRSF3), another splicing factor and partner of TDP43, acts as an upstream regulator of TDP43 to maintain CD44v isoforms and thereafter BCSC stemness. Mechanistically, SRSF3 stabilizes the mRNA of TDP43 by inhibiting nonsense-mediated decay (NMD). These findings illustrate the important role of complicated regulatory networks formed by splicing factors in TNBC progression, thus providing potential therapeutic targets from an AS perspective.
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/152453/13640
专题	科研部门_发育的印迹调控与进化学（焦保卫）
推荐引用方式 GB/T 7714	Guo, L,Ke, H,Zhang, HL,et al. TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms[J]. CELL DEATH & DISEASE,2022,13(5).
APA	Guo, L.,Ke, H.,Zhang, HL.,Zou, L.,Yang, Q.,...&Jiao, BW.(2022).TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms.CELL DEATH & DISEASE,13(5).
MLA	Guo, L,et al."TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms".CELL DEATH & DISEASE 13.5(2022).

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