Collagen type VIII alpha 1 chain (COL8A1) is a part of the collagen family and has been involved in tumor progression in numerous cancers. Nevertheless, its expression pattern, functional role, and underlying mechanisms in prostate cancer (PCa) remain largely unexplored. COL8A1 expression was analyzed using public datasets and clinical samples. Functional roles of COL8A1 in PCa cells were assessed via CCK-8, Transwell, wound healing, and flow cytometry assays. Protein interactions were assessed by co-immunoprecipitation and pull-down assays. The underlying mechanism was explored using Western blot (WB), bioinformatics analysis, and in vivo xenograft models. COL8A1 was significantly increased in PCa tissues and cell lines, and its expression related to advanced clinicopathological features and poor progression-free survival. Functional studies showed that COL8A1 promotes cell proliferation, invasion, and migration while inhibiting apoptosis. Mechanistically, COL8A1 interacts with ADAMTS2, and its modulation affects ADAMTS2 protein expression. This interaction results in stimulation of the FAK/PI3K/AKT pathway. ADAMTS2 suppression partially reversed the oncogenic effects of COL8A1 overexpression. Moreover, COL8A1 expression was positively linked to immune cell infiltration in the tumor microenvironment. In vivo experiments confirmed that COL8A1 knockdown suppresses tumor growth. Our findings identify COL8A1 as an innovative oncogenic driver in PCa that promotes tumor progression via modulation of the ADAMTS2-FAK/PI3K/AKT axis and immune infiltration. COL8A1 may be a potential prognostic biomarker and therapeutic target for PCa.
Wang et al. (Fri,) studied this question.