SRp20: A potential therapeutic target for human tumors

Wang, Han; Jiang, Yanxia

doi:10.1016/j.prp.2021.153444

Cited by 4 publications

(1 citation statement)

References 114 publications

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“…The splicing factor TDP43, which is highly expressed in various tumors, regulates many AS events and is a vital factor in breast cancer progression [ 32 – 34 ]. Several compounds affect the expression levels of SRSF3 and TDP43, and thus both molecules could act as potential therapeutic targets for tumors [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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