Speaker
Description
Cancer-associated fibroblasts (CAFs) play a key role in tumor progression by orchestrating complex signaling interactions within the tumor microenvironment. However, the regulatory architecture of CAF-mediated signaling networks remains poorly understood at the systems level. Microtubule-associated serine/threonine kinase-like (MASTL), a mitotic kinase involved in cell cycle regulation, has been implicated in gastric cancer cell proliferation, but its role in stromal signaling is unknown. Here, we investigated whether MASTL functions as a regulatory node in CAF signaling networks. Conditioned media from gastric cancer cells induced MASTL expression in CAFs, suggesting tumor-driven modulation of stromal kinase activity. Functional assays showed that MASTL silencing impaired CAF migration and tumor-promoting properties. To characterize the underlying mechanisms, we performed quantitative secretome profiling using high-resolution LC–MS/MS. Systems-level proteomic analysis identified MASTL-dependent changes in secreted factors. Network-based bioinformatic analyses highlighted VEGFA–VEGFR2 signaling as a central pathway. Consistently, CAF secretomes regulated by MASTL enhanced angiogenic activity in endothelial tube formation assays. These findings suggest that MASTL reshapes the CAF secretory signaling network to regulate tumor angiogenesis.
