Epidermal growth factor stimulates matrix metalloproteinase-9 expression and invasion in human follicular thyroid carcinoma cells through Focal adhesion kinase.
In order to further advance our knowledge of the role epidermal growth factor (EGF) plays in thyroid carcinoma, we investigated its effect on the regulation of matrix metalloproteinase-9 (MMP-9), a key enzyme that plays an important role in tumor invasion and angiogenesis. The expression of MMP-9 in EGF-treated and untreated human follicular thyroid carcinoma cells (FTC-133) was evaluated using reverse transcription-PCR, Western blot and gelatin zymography. Transient transfection and electrophoretic mobility shift assays (EMSA) were also performed to measure MMP-9 promoter activity, to identify multiple signaling pathways and to determine a proximal AP-1-binding site located between -79 to -73 base pairs upstream of the transcriptional start site that is involved in activation of MMP-9 by EGF. In the present study, we demonstrate that EGF treatment up-regulated MMP-9 expression in human follicular thyroid carcinoma cells. Expression of FAK-related non kinase (FRNK), a potent dominant-negative inhibitor of FAK, reduced FAK auto-phosphorylation and inhibited EGF-induced MMP-9 transcription and secretion leading to decreased cell invasion through Matrigel in in vitro Transwell assays. Our studies highlight the role FAK plays in promoting cell invasion through the activation of distinct signaling pathways induced by EGF with protein MMP-9 transcription and secretion in follicular thyroid carcinoma cells.
Rothhut
Bernard
B
Unité Matrice Extracellulaire et Régulations Cellulaires, Laboratory of Biochemistry, URCA, CNRS, Moulin de la Housse, 51687 Reims, France. bernard.rothhut@univ-reims.fr
Ghoneim
Christelle
C
Antonicelli
Frank
F
Soula-Rothhut
Mahdhia
M
D000236:Adenoma / Q000473:pathology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1 / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009363:Neoplasm Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000473:pathology*; D018808:Transcription Factor AP-1
D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020780:Matrix Metalloproteinase 9