Unveiling ADAMTS12: A key driver of bladder cancer progression via COL3A1-Mediated activation of the FAK/PI3K/AKT signaling pathway.

Bladder cancer (BCa) is a common and lethal disease characterized by high recurrence rates and limited treatment options. Understanding the molecular pathways of BCa progress is crucial for investigating more effective targeted therapies. While ADAMTS12 is known to contribute to cancer progression and treatment resistance, its prognostic significance and underlying mechanisms in BCa remain poorly understood. To elucidate the molecular pathways and functions of ADAMTS12 in BCa, we employed various experimental approaches, including Transwell invasion assays, flow cytometry analysis, wound-healing assays, CCK-8 assays, and a xenograft tumor model. Our results demonstrated that overexpression of ADAMTS12 significantly enhanced cell growth, migration, and invasion while inhibiting apoptosis through the activation of the FAK/PI3K/AKT signaling pathway. Conversely, the knockdown of ADAMTS12 produced the opposite effects. In vivo studies further confirmed that the inhibition of ADAMTS12 effectively suppressed tumor progression. Comprehensive bioinformatics analysis of the TCGA-BLCA dataset and protein-protein interaction networks revealed a strong positive correlation between COL3A1 and ADAMTS12, identifying COL3A1 as a potential downstream target of ADAMTS12. Additionally, we observed a significant increase in the expression levels of ADAMTS12 and COL3A1 in BCa tissues compared to healthy tissues, as confirmed by Western blotting and qRT-PCR analysis. Notably, inhibition of COL3A1 reversed the enhanced cell growth and invasion associated with ADAMTS12 overexpression and suppressed cell apoptosis. Our findings suggest that ADAMTS12 promotes BCa progression through the FAK/PI3K/AKT signaling pathway by regulating COL3A1, highlighting its potential as a valuable marker for diagnosis and prognosis in BCa.