Abstract
Epidermal growth factor (EGF) receptor (EGFR) is involved in various basic biochemical pathways and is thus thought to play an important role in cell migration. We examined the effect of EGF on motility, migration, and morphology of a human adenocarcinoma cell line CAC-1. EGF treatment increased the motility of cervical adenocarcinoma cells and promoted migration of the cells on fibronectin and type IV collagen. EGF induced morphological changes with lamellipodia during EGFR-mediated motility. The results of an immunoprecipitation study showed that EGF up-regulated the expression of alpha2beta1-integrin in a dose-dependent manner. EGF-induced cell migration was blocked by alpha2beta1-integrin antibody. Our results also showed that EGF treatment stimulated the level of tyrosine dephosphorylation of FAK, which is required for EGF-induced changes in motility, migration, and cell morphology. A tyrosine kinase inhibitor (ZD1839) blocked EGF-induced changes in cervical adenocarcinoma cells. The results suggest that EGF promotes cell motility and migration and increases the expression of alpha2beta1-integrin, possibly by decreasing FAK phosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism*
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Antibodies / pharmacology
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cell Size / drug effects
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Cell Size / physiology
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Collagen Type IV / pharmacology
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / metabolism*
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / drug effects
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ErbB Receptors / metabolism*
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Female
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Fibronectins / pharmacology
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Humans
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Integrin alpha2beta1 / antagonists & inhibitors
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Integrin alpha2beta1 / metabolism*
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Pseudopodia / drug effects
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Pseudopodia / metabolism
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Pseudopodia / ultrastructure
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tumor Cells, Cultured
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Tyrosine / metabolism
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / metabolism*
Substances
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Antibodies
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Collagen Type IV
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Enzyme Inhibitors
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Fibronectins
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Integrin alpha2beta1
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Tyrosine
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Epidermal Growth Factor
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ErbB Receptors
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human