title: Excess centrosomes disrupt endothelial cell migration via centrosome scattering.
abstract: Supernumerary centrosomes contribute to spindle defects and aneuploidy at mitosis, but the effects of excess centrosomes during interphase are poorly understood. In this paper, we show that interphase endothelial cells with even one extra centrosome exhibit a cascade of defects, resulting in disrupted cell migration and abnormal blood vessel sprouting. Endothelial cells with supernumerary centrosomes had increased centrosome scattering and reduced microtubule (MT) nucleation capacity that correlated with decreased Golgi integrity and randomized vesicle trafficking, and ablation of excess centrosomes partially rescued these parameters. Mechanistically, tumor endothelial cells with supernumerary centrosomes had less centrosome-localized γ-tubulin, and Plk1 blockade prevented MT growth, whereas overexpression rescued centrosome γ-tubulin levels and centrosome dynamics. These data support a model whereby centrosome-MT interactions during interphase are important for centrosome clustering and cell polarity and further suggest that disruption of interphase cell behavior by supernumerary centrosomes contributes to pathology independent of mitotic effects.
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Erich J
authors: EJ
authors: Kushner
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Luke S
authors: LS
authors: Ferro
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Jie-Yu
authors: JY
authors: Liu
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Jessica R
authors: JR
authors: Durrant
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Stephen L
authors: SL
authors: Rogers
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors: Andrew C
authors: AC
authors: Dudley
authors: Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Department of Biology, McAllister Heart Institute, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 bautch@med.unc.edu.
authors: Victoria L
authors: VL
authors: Bautch
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D002465:Cell Movement; D018385:Centrosome / Q000502:physiology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000648:ultrastructure*; D006056:Golgi Apparatus / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007399:Interphase; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured