Knockdown of BAP31 Suppresses Tumorigenesis and Stemness in Breast Cancer Cells via the Hippo Pathway.

The enhancement of stemness in cancer cells is correlated with the malignancy level in human cancers. B cell receptor-associated protein 31 (BAP31) has been implicated in tumor progression; however, its specific role in breast cancer remains unclear. This study aimed to elucidate the biological function and molecular mechanisms of BAP31 in tumorigenesis and cancer stemness. Cancer stemness was assessed through tumor sphere formation and flow cytometry assays. Western blot analysis was employed to examine alterations in core stemness factors in BAP31 knockdown cell lines, in order to explore potential underlying mechanisms. Finally, we explored the role of BAP31 by developing xenograft models using nude mice in vivo. Our findings revealed that BAP31 expression was elevated in breast cancer cells, and its knockdown led to a decrease in both sphere formation and the CD44+CD24- population. Furthermore, the knockdown of BAP31 significantly diminished the expression of core stemness factors, such as Sox2 and c-Myc, in breast cancer cells in vitro. Consistently, the suppression of BAP31 markedly inhibited the tumorigenicity and stemness of breast cancer in vivo. The functional analysis further indicated that the knockdown of BAP31 diminishes stemness by activating the Hippo pathway kinase MST1 and inhibiting the transcription factor YAP. Notably, our study was the first to demonstrate that BAP31 interacts with PCMT1, a direct negative regulator of MST1 kinase. These findings identify BAP31 as a regulator of the Hippo pathway, highlighting its critical role in breast cancer tumorigenesis and stemness. Consequently, BAP31 emerges as a potential therapeutic target for this malignancy.