PNO1 enhances ovarian cancer cell growth, invasion, and stemness via activating the AKT/Wnt/β-catenin pathway

PNO1, a key promoter of oncogenesis, is often characterized by its aberrant expression in both colorectal and esophageal cancers, markedly accelerating their progression. Nonetheless, the role of PNO1 in ovarian cancer and its underlying mechanisms remain unexplored comprehensively. In addition to the abnormal PNO1 expression in ovarian cancer tissues by The Cancer Genome Atlas (TCGA) database, the clinical data examinations indicated its strong association with lower survival rates among ovarian cancer patients. Considering the crucial role of the AKT signaling pathway, we hypothesized that PNO1 might drive the progression of ovarian cancer by modulating the AKT pathway. To validate this hypothesis, experiments were conducted to silence PNO1 in ovarian cancer cells. These findings demonstrated that PNO1 silencing markedly reduced the proliferation and invasion capabilities of ovarian cancer cell lines, triggering their apoptosis. Moreover, the PNO1 suppression significantly decreased the expression levels of p-AKT, GSK-3 beta, and active beta-catenin proteins, further confirming the regulatory correlation between PNO1 and the AKT/Wnt/beta-catenin pathway. The oncogenic effects mediated by the PNO1-activated Wnt/beta-catenin pathway were counteracted by inhibitors of the AKT signaling pathway. Further, the subcutaneous xenograft tumor assays in vivo validated that PNO1 silencing decreased the tumorigenic potential of ovarian cancer cells. In summary, this study has elucidated that the upregulation of PNO1 modulated the tumorigenic role of the AKT/Wnt/beta-catenin pathway in ovarian cancer, offering new insights into its oncogenic function.