Investigating the Role of ATP6AP1 in Modulating Breast Cancer Proliferation, Migration, and Drug Sensitivity

Abstract Breast cancer (BRCA) remains one of the most prevalent malignancies affecting women globally. Despite significant advancements in diagnostic tools and therapeutic strategies, the marked heterogeneity of BRCA leads to considerable variability in patient prognosis. ATP6AP1, functioning as a subunit of the V-ATPase (vacuolar-type H+-ATPase), is a transmembrane protein crucial for the assembly and regulation of this proton pump. To elucidate the role of ATP6AP1 in BRCA, we conducted an in-depth analysis of multiple public databases. This investigation aimed to establish correlations between ATP6AP1 expression and clinicopathological features, alongside performing survival prognostic analyses. The expression levels of ATP6AP1 in breast cancer tissues and cell lines were subsequently validated using quantitative reverse transcription polymerase chain reaction (qrt-PCR), Western blotting, and immunohistochemistry (IHC). Further experiments, including clone formation, scratch, Transwell migration/invasion assays, and EdU proliferation assays, were employed to assess the impact of ATP6AP1 on cancer cell proliferation, migration, and invasion. Additionally, the relationship between ATP6AP1 and drug sensitivity was predicted using the CellMiner database. Our overarching goal was to delineate the potential functions of ATP6AP1 in BRCA and to understand its implications for drug responsiveness. We observed significantly elevated ATP6AP1 expression in BRCA tissues and cell lines, which strongly correlated with poor patient prognosis. Crucially, the knockdown of ATP6AP1 markedly suppressed the viability and proliferative capacity of BRCA cells. In conclusion, ATP6AP1 emerges as a prognostic biomarker for BRCA and represents a promising therapeutic target.