Endothelial metastasis-associated protein 1 (MTA1) is an essential molecule for angiogenesis

Our previous study revealed that metastasis-associated protein 1 (MTA1), expressed in endothelial cells acts as a factor promoting tube formation. In this study, we aimed to clarify the importance of MTA1 in tube formation using MTA1-knockout endothelial cells (MTA1-KO MSS31 cells). Tube formation was strongly suppressed in MTA1-KO MSS31 cells, whereas MTA1-overexpressed MTA1-KO MSS31 cells regained the ability to form tube-like structures. Furthermore, MTA1-KO MSS31 cells showed higher phosphorylation of non-muscle myosin heavy chain IIa (NMIIa), which resulted in suppression of tube formation; this was attributed to a decrease of MTA1- S100 calcium-binding protein A4 (S100A4) 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 is an essential molecule for angiogenesis, and that it may be involved in different steps of the angiogenic process compared to the VEGF-VEGF receptor 2 (VEGFR2) pathway. Our findings showed that endothelial MTA1 and its pathway are promising targets for inhibiting tumor angiogenesis, supporting the development of MTA1-based anti-angiogenic therapies.