Silencing of fibronectin type III domain-containing protein 3A (FNDC3A) attenuates epithelial-to-mesenchymal transition (EMT), cancer invasion, and stemness in triple-negative breast cancer (TNBC)

Currently, there are no effective therapeutic targets for triple-negative breast cancer (TNBC), including hormonal therapy, and it has a poor prognosis because of its rapid proliferation, high invasiveness, and metastatic potential. Therefore, it is expected that the elucidation of the characteristics of TNBC at the molecular level may lead to the development of new therapeutic drugs. In this study, Kaplan-Meier curve analysis showed that high expression levels of fibronectin type III domain-containing protein 3A (FNDC3A) were associated with poor overall survival in patients with TNBC. Furthermore, FNDC3A knockdown was found to suppress the epithelialto-mesenchymal transition (EMT) and invasion potential as well as the stemness in several TNBC cell lines. In addition, RNA-seq analysis revealed that FNDC3A suppression inhibited the expression of Yes-associated protein 1 (YAP1) and its target genes, which have been reported to regulate cancer cell invasion and stemness. These results suggest that FNDC3A is a novel factor that plays an important role in the malignant progression of TNBC by maintaining cancer stemness and promoting cell invasion and that its function may involve the YAP1 pathway regulation. Therefore, FNDC3A is expected to become a potential therapeutic target for patients with TNBC.