COL6A3 drives tumor progression and predicts prognosis in cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CESC) is the most prevalent histological subtype of cervical cancer, and patients with advanced or metastatic disease still face a dismal prognosis. Collagen type Ⅵ alpha 3 (COL6A3), a key component of the extracellular matrix, has been shown to promote tumor progression in various malignancies, but its role in CESC remains unclear. A total of 20 paired CESC tissues and adjacent normal cervical tissues were collected for real-time PCR and Western blot analysis. Additionally, 179 paraffin-embedded CESC tissues from patients who underwent radical resection were enrolled to analyze the correlation between COL6A3 expression and clinicopathological features, as well as patient prognosis. Stable COL6A3 overexpression (SiHa cells) and knockdown (C-33A cells) cell lines were established, and functional experiments including CCK-8, colony formation, transwell and cell scratch assays were performed to explore the role of COL6A3 in CESC. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related markers. COL6A3 mRNA and protein levels were significantly upregulated in CESC tissues compared with adjacent normal tissues. High COL6A3 expression was closely associated with pT status, pN status, and FIGO stage, and predicted poor overall survival in CESC patients. Multivariate Cox regression analysis confirmed that COL6A3 was an independent prognostic factor for CESC. Functional experiments showed that COL6A3 overexpression significantly promoted the proliferation, migration, and invasion of SiHa cells, while COL6A3 knockdown inhibited these biological behaviors in C-33A cells. Moreover, COL6A3 overexpression downregulated E-cadherin and upregulated N-cadherin and Vimentin, suggesting that COL6A3 promotes CESC cell migration and invasion by inducing EMT. COL6A3 functions as an oncogenic driver in CESC, promoting cell proliferation, migration, and invasion, and may serve as a potential prognostic biomarker and therapeutic target for CESC.