Of Hdac6 To The Relationship Between Endothelial Cell Migration

Cell migration is a common process in the development and maintenance of multicellular organisms and disease occurrence. Embryonic morphogenesis, wound healing, immune responses, and tumor invasion all require the orchestrated movement of cells in a particular direction to a specific location. It is reported that histone deacetylase 6, which is abbreviated as HDAC6, is involved in cell migration. In this study, we focus on vascular endothelial cells, which play important roles in physiological and pathological processes of the vascular system. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for the control of vascular diseases. Moreover, the migration of vascular endothelial cells is expected to become an important target for improving cancer treatment, because it plays key roles in tumor growth, invasion and metastasis.In this study, we find that vascular endothelial cell migration is regulated by HDAC6, in a deacetylase activity-dependent manner. The migration ability of vascular endothelial cells is significantly decreased by inhibition of HDAC6 activity with specific inhibitors or knockdown of HDAC6 expression with siRNAs. Further study shows that overexpression of HDAC6 can restore the migration of siRNA-transfected cells. These results indicate that HDAC6 plays a key role in the migration of vascular endothelial cells.Cell polarization is critical for the migration of cells. We find in this study that HDAC6 enhances vascular endothelial cell migration by promoting cell polarization and adhesion turnover. We have also investigated the mechanism of how HDAC6 exerts its effect on cell migration. Our data show that HDAC6 could interact with EB1 via its second HDAC domain, suggesting that EB1 may acts downstream of HDAC6, and trigger the 'search and capture' mechanisms. Our study also reveals that HDAC6 is critical for blood tube formation. Taken together, our results support the notion that HDAC6-targeted drugs might be useful for the treatment of vascular diseases and cancer metastasis.