Cep70 contributes to angiogenesis by modulating microtubule rearrangement and stimulating cell polarization and migration

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2012-04, Vol.11 (8), p.1554-1563
• Main Authors: Shi, Xingjuan, Liu, Min, Li, Dengwen, Wang, Jun, Aneja, Ritu, Zhou, Jun
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; Binding; Biology; Bioscience; Calcium; Cancer; cdc42 GTP-Binding Protein - metabolism; Cell; cell migration; Cell Movement; Cell Polarity; cell polarization; Cell Shape; Cep70; Cycle; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Landes; Mice; microtubule; Microtubule-Associated Proteins - antagonists & inhibitors; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neovascularization, Physiologic; Organogenesis; Proteins; rac1 GTP-Binding Protein - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Tubulin Modulators - metabolism; Wound Healing
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.19954

Centrosomal proteins intricately regulate diverse microtubule-mediated cellular activities, including cell polarization and migration. However, the direct participation of these proteins in angiogenesis, which involves vascular endothelial cell migration from preexisting blood vessels, remains elusive. Here we show that the centrosomal protein Cep70 is necessary for angiogenic response in mice. This protein is also required for tube formation and capillary sprouting in vitro from vascular endothelial cells. Wound healing and transwell assays reveal that Cep70 plays a significant role in endothelial cell migration. Depletion of Cep70 results in severe defects in membrane ruffling and centrosome reorientation, indicating a requirement for this protein in cell polarization. In addition, Cep70 is critically involved in microtubule rearrangement in response to the migratory stimulus. Our data further demonstrate that Cep70 is important for Cdc42 and Rac1 activation to promote angiogenesis. These findings thus establish Cep70 as a crucial regulator of the angiogenic process and emphasize the significance of microtubule rearrangement and cell polarization and migration in angiogenesis.