title: Mechanisms of gelsolin-dependent and -independent EGF-stimulated cell motility in a human lung epithelial cell line.
abstract: Acquisition of motility is an important step in malignant progression of tumor cells and involves dynamic changes in actin filament architecture orchestrated by many actin binding proteins. A role for the actin-binding protein gelsolin has been demonstrated in fibroblast motility. In this report, we investigated the role of gelsolin in bronchial epithelial cell motility. The non-tumorigenic bronchial epithelial cell line, NL20 migrated towards EGF in a modified Boyden chamber cell motility assay. However, the tumorigenic NL20-TA cell line derived from the NL20 cells and lacking gelsolin, did not migrate towards EGF. Ectopic expression of gelsolin in NL20-TA cells restored the EGF response, while motility of NL20-TA derived cells towards serum, PDGF, and fibronectin was independent of gelsolin expression. PI3-kinase inhibition failed to block EGF-stimulated motility in gelsolin transfected NL20-TA cells. Furthermore, EGF stimulated a motility response in cells lacking gelsolin in the presence of fibronectin or fibrinogen that was blocked with PI3-kinase inhibition. Thus, EGF-stimulated motility in NL20 cells and its derivatives are gelsolin dependent and PI3-kinase independent, while fibronectin and fibrinogen enhances EGF-stimulated motility through a pathway independent of gelsolin and dependent upon PI3-kinase.
authors.affiliation: Hematology Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. alader@rics.bwh.harvard.edu
authors.forename: Alan S
authors.initials: AS
authors.lastname: Lader
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Gregor
authors.initials: G
authors.lastname: Cicchetti
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D044967:Serum / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002867:Chromones; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D004963:Estrenes; D005353:Fibronectins; D018260:Gelsolin; D009025:Morpholines; D010982:Platelet-Derived Growth Factor; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004815:Epidermal Growth Factor; D005340:Fibrinogen; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D002118:Calcium