The aryl hydrocarbon receptor regulates focal adhesion sites through a non-genomic FAK/Src pathway.
The aryl hydrocarbon receptor (AhR) is commonly described as a transcription factor, which regulates xenobiotic-metabolizing enzymes. Recent studies have suggested that the binding of ligands to the AhR also activates the Src kinase. In this manuscript, we show that the AhR, through the activation of Src, activates focal adhesion kinase (FAK) and promotes integrin clustering. These effects contribute to cell migration. Further, we show that the activation of the AhR increases the interaction of FAK with the metastatic marker, HEF1/NEDD9/CAS-L, and the expression of several integrins. Xenobiotic exposure, thus, may contribute to novel cell-migratory programs.
INSERM UMR-S 747, Toxicologie Pharmacologie et Signalisation Cellulaire, Paris, France.
C
C
Tomkiewicz
L
L
Herry
L-C
LC
Bui
C
C
Métayer
M
M
Bourdeloux
R
R
Barouki
X
X
Coumoul
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019012:Integrin beta1; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases