Modulation of hepatocyte growth factor-induced scattering of HT29 colon carcinoma cells. Involvement of the MAPK pathway.
Hepatocyte growth factor (HGF)/scatter factor modulates the motility of HT29 colon carcinoma cells in vitro by inducing morphological changes that depend on the type of extra-cellular matrix (ECM) ligand; HGF-induced scattering of HT29 cells is observed if cells are grown on plastic coated with serum proteins but not laminin. The absence of scattering correlates with a lack of cell spreading on laminin and it is not due to impaired HGF induced tyrosine phosphorylation of the E-cadherin/desmosome component, (gamma)-catenin, or lack of activation of mitogen activated protein kinase (MAPK). Treatment of HT29 cells with phorbol 12-myristate, 13-acetate (PMA), but not arachidonic acid, restored the ability of the cells to spread on laminin in an integrin-dependent manner. Moreover, the addition of both PMA and HGF restored the ability of these cells to scatter on laminin in a synergistic manner. This event correlated with increased tyrosine phosphorylation of paxillin and activation of MAPK. Moreover, when the MEK (MAPK kinase)/MAPK pathway was blocked by the MEK inhibitor PD098059, HGF-induced scattering of HT29 cells was blocked. Thus, HGF modulation of HT29 cell motility is regulated by both integrin and growth factor-dependent signaling and implicates MAPK in the modulation of intercellular adhesion and epithelial cell motility.
Herrera
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Department of Cell Biology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Co, Ann Arbor, MI 48105, USA. herrerr@aa.wl.com
D000199:Actins / Q000032:analysis; D016718:Arachidonic Acid / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D003896:Desmosomes / Q000737:chemistry / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019073:HT29 Cells / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000199:Actins; D002273:Carcinogens; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D005419:Flavonoids; D007797:Laminin; D016718:Arachidonic Acid; D017228:Hepatocyte Growth Factor; D003094:Collagen; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one