Tumor-derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-duplication
Publication Date
12-15-2016
Document Type
Article
Organizational Units
Biological Sciences
Keywords
Endothelial cells, Abnormal vessel function, Hypoxia, Over-duplicated, Centrosomes
Abstract
Approximately 30% of tumor endothelial cells have over-duplicated (>2) centrosomes, which may contribute to abnormal vessel function and drug resistance. Elevated levels of vascular endothelial growth factor A induce excess centrosomes in endothelial cells, but how other features of the tumor environment affect centrosome over-duplication is not known. To test this, we treated endothelial cells with tumor-derived factors, hypoxia, or reduced p53, and assessed centrosome numbers. We found that hypoxia and elevated levels of bone morphogenetic protein 2, 6 and 7 induced excess centrosomes in endothelial cells through BMPR1A and likely via SMAD signaling. In contrast, inflammatory mediators IL-8 and lipopolysaccharide did not induce excess centrosomes. Finally, down-regulation in endothelial cells of p53, a critical regulator of DNA damage and proliferation, caused centrosome over-duplication. Our findings suggest that some tumor-derived factors and genetic changes in endothelial cells contribute to excess centrosomes in tumor endothelial cells.
Publication Statement
Copyright held by author or publisher. User is responsible for all copyright compliance.
Recommended Citation
Yu, Zhixian, et al. “Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication.” PloS One, vol. 11, no. 12, 2016, p. e0168334. doi: 10.1371/journal.pone.0168334.