Arachidonic acid promotes FAK activation and migration in MDA-MB-231 breast cancer cells.
Arachidonic acid (AA) is a common dietary n-6 polyunsaturated fatty acid that is present in an esterified form in cell membrane phospholipids, and it might be present in the extracellular microenvironment. In particular, AA promotes MAPK activation and mediates the adhesion of MDA-MB-435 breast cancer cells to type IV collagen. However, the signal transduction pathways mediated by AA have not been studied in detail. Our results demonstrate that stimulation of MDA-MB-231 breast cancer cells with AA promotes an increase in the phoshorylation of Src and FAK, as revealed by site-specific antibodies that recognized the phosphorylation state of Src at Tyr-418, and of FAK at tyrosine-397 and in vitro kinase assays. In addition, AA also induces an increase in the migration of MDA-MB-231 cells. In contrast, AA does not induce phosphorylation of FAK and an increase in cell migration of non-tumorigenic epithelial cells MCF10A. Inhibition of Gi/Go proteins, LOX and Src activity prevent FAK activation and cell migration. In conclusion, our results demonstrate, for the first time, that Gi/Go proteins, LOX and Src play an important role in FAK activation and cell migration induced by AA in MDA-MB-231 breast cancer cells.
Navarro-Tito
Napoleon
N
Departamento de Biologia Celular, Cinvestav-IPN, Av IPN # 2508, San Pedro Zacatenco Mexico, DF 07360 Mexico.
Robledo
Teresa
T
Salazar
Eduardo Perez
EP
D016718:Arachidonic Acid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D043562:Receptors, G-Protein-Coupled; D051127:Scavenger Receptors, Class E; D016718:Arachidonic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go