CRB2 Facilitates Epithelial Ovarian Cancer Progression by Inducing Polarity Changes via Activation of the Wnt/PCP Signalling Pathway

Abstract

Ovarian cancer exhibits high molecular heterogeneity and metastatic potential, contributing to its status as a leading cause of gynecologic cancer mortality. Cell polarity is essential in tumorigenesis, yet the role of Crumbs family proteins (CRBs), key regulators of apical–basal polarity, in epithelial ovarian cancer (EOC) remains unclear. In this study, we analysed CRB expression profiles using TCGA and GEO datasets, and validated our findings through immunohistochemical staining of ovarian tumour tissue microarrays. Among CRBs, CRB2 was significantly overexpressed in EOC tissues and correlated with poor patient prognosis. Functional assays revealed that CRB2 enhances ovarian cancer cell proliferation, migration, and invasion, while suppressing apoptosis. Immunofluorescence staining of planar cell polarity markers demonstrated that CRB2 induces polarity alterations in EOC cells. Furthermore, Western blot analysis suggested that CRB2 may activate the Wnt/planar cell polarity (PCP) signalling pathway, contributing to tumour progression. These findings identify CRB2 as a key modulator of cell polarity and a potential driver of EOC aggressiveness. CRB2 may serve as a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer.