MTA1, a metastasis-associated protein, in endothelial cells is an essential molecule for angiogenesis

Our previous study revealed that metastasis-associated protein 1 (MTA1), which is expressed in vascular endothelial cells, acts as a tube formation promoting factor. The present study aimed to clarify the importance of MTA1 expression in tube formation using MTA1-knockout (KO) endothelial cells (MTA1-KO MSS31 cells). Tube formation was significantly suppressed in MTA1-KO MSS31 cells, whereas MTA1-overexpression MTA1-KO MSS31 cells regained the ability to form tube-like structures. In addition, western blotting analysis revealed that MTA1-KO MSS31 cells showed significantly higher levels of phosphorylation of non-muscle myosin heavy chain IIa, which resulted in suppression of tube formation. This effect was attributed to a decrease of MTA1/S100 calcium-binding protein A4 complex formation. Moreover, inhibition of tube formation in MTA1-KO MSS31 cells could not be rescued by stimulation with vascular endothelial growth factor (VEGF). These results demonstrated that MTA1 may serve as an essential molecule for angiogenesis in endothelial cells and be involved in different steps of the angiogenic process compared with the VEGF/VEGF receptor 2 pathway. The findings showed that endothelial MTA1 and its pathway may serve as promising targets for inhibiting tumor angiogenesis, further supporting the development of MTA1-based antiangiogenic therapies.