title: Structure and biomechanics of the endothelial transcellular circumferential invasion array in tumor invasion.
abstract: Cancer cells breach the endothelium not only through cell-cell junctions but also via individual endothelial cells (ECs), or transcellular invasion. The underlying EC forms a circular structure around the transcellular invasion pore that is dependent on myosin light chain kinase (MLCK) and myosin II regulatory light chain (RLC) phosphorylation. Here we offer mechanistic insights into transcellular invasive array formation amid persistent tensile force from activated EC myosin. Fluorescence recovery after photobleaching (FRAP) experiments, sarcomeric distance measurements using super-resolution microscopy and electron microscopy provide details about the nature of the myosin II invasion array. To probe the relationship between biomechanical forces and the tension required to maintain the curvature of contractile filaments, we targeted individual actin-myosin fibers at the invasion site for photoablation. We showed that adjacent filaments rapidly replace the ablat11ed structures. We propose that the transcellular circumferential invasion array (TCIA) provides the necessary constraint within the EC to blunt the radial compression from the invading cancer cell.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Constadina
authors.initials: C
authors.lastname: Arvanitis
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America ; Center for Advanced Microscopy, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Satya
authors.initials: S
authors.lastname: Khuon
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Spann
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America ; Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ridge
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America ; Center for Advanced Microscopy, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Teng-Leong
authors.initials: TL
authors.lastname: Chew
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000704:Analysis of Variance; D001696:Biomechanical Phenomena; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D036681:Fluorescence Recovery After Photobleaching; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053685:Laser Therapy; D008856:Microscopy, Fluorescence; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010766:Phosphorylation; D013718:Tensile Strength; D057688:Transcellular Cell Migration / Q000502:physiology*
chemical_list: D018994:Myosin Light Chains; D000205:Actomyosin; D009219:Myosin-Light-Chain Kinase