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

ABSTRACT: 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),

SUBMITTER: Guo L 

PROVIDER: S-EPMC9065105 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature