NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis

Abstract Metastasis is a major cause of death in individuals suffering from triple-negative breast cancer. Alternative splicing of mRNA precursor allows cancer cells to create different protein isoforms which may promote metastasis. Quantitative proteomic analysis of primary and metastatic breast cancer cells revealed that nuclear speckle-related protein 70 (NSrp70) was significantly downregulated in highly metastatic cells. Downregulation of NSrp70 promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of TGF-beta receptor 1(TβR1) through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition (EMT) phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 may serve as a metastasis suppressor.