PCDH8 promotes malignant progression of cervical cancer via the Wnt/β-catenin axis

Abstract Objectives Dysregulated expression of protocadherin 8 (PCDH8) has been observed in several malignancies and is associated with cancer progression. Yet, its role in cervical carcinogenesis requires systematic investigation. This investigation seeks to elucidate the molecular mechanisms of PCDH8-mediated malignant phenotypic regulation in cervical cancer, thereby identifying novel biomarkers for early diagnosis and providing a foundation for the development of targeted therapies. Methods Metastasis-associated genes were determined by differential expression analysis on the Cancer Genome Atlas (TCGA) cervical cancer database. PCDH8 overexpression models were established in SiHa cells, and knockdown models were established in HeLa cells. Transfection efficiency and molecular mechanisms were assessed. Cell functions were evaluated. Gene Set Enrichment Analysis (GSEA) identified PCDH8-related signaling pathways. TOP/FOP dual-luciferase reporter system quantified pathway activity. β-catenin functional intervention experiments validated PCDH8-mediated regulatory mechanisms. Results Cervical cancer datasets from TCGA revealed significant PCDH8 upregulation in metastatic (n=68) vs. the non-metastatic (n=79). High PCDH8 expression was linked to reduced median overall survival (n=55; p=0.024) and metastasis-free survival (n=55; p=0.006). PCDH8 overexpression enhanced the proliferative, migratory, and invasive capacities of cervical cancer cells; in contrast, PCDH8 knockdown attenuated these outcomes. Mechanistically, PCDH8 stimulated the Wnt/β-catenin pathway, upregulating metalloproteinase-7 (MMP7), Cyclin D1, and c-Myc to drive malignant phenotypes of cervical cancer cells. However, β-catenin knockdown reversed these effects. Conclusions PCDH8 drives the malignant phenotypes of cervical cancer cells via activating the Wnt/β-catenin pathway. This study identifies a potential therapeutic target and suggests potential clinical implications for improving cervical cancer patient prognosis.