A Functional Role of S100A4/Non-Muscle Myosin IIA Axis for Pro-Tumorigenic Vascular Functions in Glioblastoma

The study investigated the role of the S100A4/non-muscle myosin IIA (NMIIA) axis in glioblastoma (GBM) tumor progression and vasculogenesis using 94 GBM samples. It was found that overexpression of S100A4 and NMIIA was associated with increased microvascular densities in non-pseudopalisading perinecrotic lesions. S100A4(+)/HIF-1α(-) GBM cells were recruited to preexisting vessels, while S100A4(+)/HIF-1α(+) cells near vascular-rich areas showed elevated VEGFA mRNA expression. High S100A4 expression correlated with worse overall and progression-free survival in patients. Knockdown of S100A4 reduced cell migration, whereas NMIIA inhibition had the opposite effect. The findings suggested that S100A4 and NMIIA interactions promoted tumor progression by enhancing pro-tumorigenic vascular functions.