CST4 promotes EMT and tumor progression in ovarian cancer via Wnt/β-catenin signaling.

BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecologic malignancies, largely due to late diagnosis, high metastatic potential, and chemoresistance. Cystatin S (CST4) has been implicated in the tumor progression of several cancers, but its role in OC remains unclear. This study aims to investigate the expression, clinical significance, and functional role of CST4 in OC, particularly its involvement in epithelial-mesenchymal transition (EMT) via the Wnt/β-catenin signaling pathway. METHODS: Immunohistochemistry (IHC) was performed on 102 °C tissues and 20 normal ovarian tissues to assess CST4 expression. Through Kaplan-Meier analysis and Cox regression analysis, the association between CST4 expression and clinical pathological features, prognosis and survival outcomes was investigated. To investigate the functional role of CST4, small interfering RNA (siRNA) was used to silence CST4 expression in HEY and HO-8910 cell lines. Following CST4 knockdown, cell proliferation was assessed using CCK-8 assays and colony formation assays, while migratory and invasive capacities were evaluated through wound healing and transwell invasion assays, respectively. In addition, western blotting was employed to examine the expression of epithelial-mesenchymal transition (EMT)-related markers and key proteins involved in the Wnt/β-catenin signaling pathway. RESULTS: Compared with normal ovarian tissue, the expression of CST4 in OC tissues was significantly increased, and it was associated with more advanced FIGO stages, elevated CA125 levels, platinum resistance, and poor prognosis. High CST4 expression was identified as an independent prognostic factor for reducing overall and progression-free survival. Functional assays showed that CST4 knockdown suppressed OC cell proliferation, migration, and invasion. Mechanistically, CST4 silencing inhibited the Wnt/β-catenin signaling pathway and reversed the expression of EMT markers. CONCLUSIONS: CST4 is a novel oncogenic regulator in OC that promotes EMT and tumor aggressiveness via the Wnt/β-catenin signaling pathway. It may serve as an independent prognostic biomarker and potential therapeutic target for OC.