title: Localization and activity of calmodulin is involved in cell-cell adhesion of tumor cells and endothelial cells in response to hypoxic stress.
abstract: Adhesion of tumor cells to endothelial cells is known to be involved in the hematogenous metastasis of cancer, which is regulated by hypoxia. Hypoxia is able to induce a significant increase in free intracellular Ca2+ levels in both tumor cells and endothelial cells. Here, we investigate the regulatory effects of calmodulin (CaM), an intracellular calcium mediator, on tumor cell-endothelial cell adhesion under hypoxic conditions. Hypoxia facilitates HeLa cell-ECV304 endothelial cell adhesion, and results in actin cytoskeleton rearrangement in both endothelial cells and tumor cells. Suppression of CaM activation by CaM inhibitor W-7 disrupts actin cytoskeleton organization and CaM distribution in the cell-cell contact region, and thus inhibits cell-cell adhesion. CaM inhibitor also downregulates hypoxia-induced HIF-1-dependent gene expression. These results suggest that the Ca2+ -CaM signaling pathway might be involved in tumor cell-endothelial cell adhesion, and that co-localization of CaM and actin at cell-cell contact regions might be essential for this process under hypoxic stress.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing, PR China.
authors.forename: W-G
authors.initials: WG
authors.lastname: Shen
authors.forename: W-X
authors.initials: WX
authors.lastname: Peng
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: J-F
authors.initials: JF
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Dai
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: F-Y
authors.initials: FY
authors.lastname: Pan
authors.forename: C-J
authors.initials: CJ
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D002147:Calmodulin; D051793:Hypoxia-Inducible Factor 1; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C017967:W 7; D017871:Calcium-Calmodulin-Dependent Protein Kinases