MTA1, a metastasis‑associated protein, in endothelial cells is an essential molecule for angiogenesis.
Ishikawa M, Osaki M, Uno N, Ohira T, Kugoh H, Okada F.
Molecular medicine reports. 2022; 25(1):

Abstract

Our previous study revealed that metastasisassociated 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 MTA1knockout (KO) endothelial cells (MTA1KO MSS31 cells). Tube formation was significantly suppressed in MTA1KO MSS31 cells, whereas MTA1overexpression MTA1KO MSS31 cells regained the ability to form tubelike structures. In addition, western blotting analysis revealed that MTA1KO MSS31 cells showed significantly higher levels of phosphorylation of nonmuscle myosin heavy chain IIa, which resulted in suppression of tube formation. This effect was attributed to a decrease of MTA1/S100 calciumbinding protein A4 complex formation. Moreover, inhibition of tube formation in MTA1KO 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 MTA1based antiangiogenic therapies.



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