COL6A2 drives clear cell renal cell carcinoma progression via integrin-dependent modulation of Wnt/β-catenin signaling

作者：Xing Ji, Yongyang Yun, Zhenpeng Zhu, Tianyu Wu, Mingjian Ruan, Yu Fan, Qian Zhang · 发表于：Journal of Cancer · 年份：2025 · DOI：10.7150/jca.120607 · 被引用次数：1 · 研究领域：Cell Adhesion Molecules Research、Wnt/β-catenin signaling in development and cancer、Angiogenesis and VEGF in Cancer

Introduction:The mechanistic role of COL6A2, an extracellular matrix protein, in clear cell renal cell carcinoma (ccRCC) is largely unexplored.This study aimed to investigate COL6A2 expression, its prognostic value, biological functions, and underlying molecular mechanisms in ccRCC.Methods: COL6A2 expression was analyzed in ccRCC tissues and cell lines using public datasets and Western blotting on clinical samples and cell lines.Prognostic associations were evaluated using TCGA-KIRC data via clinicopathological correlations, Kaplan-Meier survival, and Cox regression analyses.Functional effects of COL6A2 knockdown in ccRCC cells were assessed by CCK-8, wound healing, Transwell, and Western blot analysis of EMT-associated proteins.Mechanistic investigations involved bioinformatic analysis, co-immunoprecipitation, Western blotting for Wnt/β-catenin pathway proteins, integrin blockade, and rescue experiments with the Wnt/β-catenin activator.Results: COL6A2 mRNA and protein were significantly upregulated in ccRCC tissues and cell lines.High COL6A2 expression correlated with aggressive clinicopathological features and independently predicted poorer prognosis.COL6A2 knockdown significantly inhibited ccRCC cell proliferation, migration, invasion, and reversed epithelial-mesenchymal transition (EMT).Mechanistically, COL6A2 was found to physically interact with integrin β1, thereby activating the Wnt/β-catenin signaling pathway to induce EMT.Rescue experiments confirmed the role of thi...