Background: Centromere protein A (CENPA) is a histone H3 variant essential for centromere function and has been implicated in tumorigenesis in several cancers. However, its clinical significance and biological role in endometrial cancer (EC) remain poorly characterized. This study aimed to elucidate the oncogenic function and underlying mechanisms of CENPA in EC progression. Methods: CENPA expression and its correlation with patient survival were analyzed using clinical datasets and tissue samples. Gain- and loss-of-function assays were performed to evaluate the effects of CENPA on EC cell proliferation, migration, and invasion. Metabolic assays, protein interaction studies, and in vivo xenograft models were utilized to investigate the molecular mechanisms driving CENPA-mediated tumorigenesis. Results: CENPA was significantly upregulated in EC tissues compared to normal endometrium, and high expression correlated with poor overall survival. Functionally, CENPA overexpression promoted, while its silencing suppressed, EC cell growth and metastasis. Mechanistically, CENPA facilitated metabolic reprogramming by enhancing aerobic glycolysis. We identified Yin Yang 1 (YY1) as a direct binding partner of CENPA. CENPA stabilized YY1 protein levels by inhibiting its proteasomal degradation. Importantly, YY1 knockdown rescued the glycolytic and tumorigenic phenotypes induced by CENPA both in vitro and in vivo. Conclusions: Our findings establish CENPA as a critical oncogenic driver in EC that functions by stabilizing YY1 to promote metabolic reprogramming. The CENPA-YY1 axis may represent a potential therapeutic target for EC.
Wang et al. (Wed,) studied this question.