Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene expression.
Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitronectin yet requires protein kinase C (PKC) activation for migration on this ligand. Here we report that this PKC-dependent cell motility event requires NF-kappaB-dependent transcription. Specifically, a component within nuclear extracts prepared from PKC-stimulated FG cells exhibited a significant increase in binding activity to a synthetic oligonucleotide containing a consensus kappa B sequence. These nuclear DNA-binding complexes were shown to be comprised of p65 and p50 NF-kappaB/rel family members and appeared functionally active because they promoted transcription of a reporter construct containing a kappa B site. The NF-kappa B activation event was directly linked to the alpha v beta 5 motility response because the NF-kappa B-binding oligonucleotide, when introduced into FG cells, inhibited cell migration on vitronectin but not on collagen and had no effect on cell adhesion to either ligand. These results suggest that the detected DNA-binding complexes interact with kappa B transcriptional elements to regulate gene expression required for alpha v beta 5-dependent cell motility on vitronectin.
Yebra
M
M
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Filardo
E J
EJ
Bayna
E M
EM
Kawahara
E
E
Becker
J C
JC
Cheresh
D A
DA
D001483:Base Sequence; D002277:Carcinoma / Q000503:physiopathology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D011493:Protein Kinase C / Q000502:physiology; D019030:Receptors, Vitronectin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D019096:Vitronectin
D004273:DNA, Neoplasm; D016023:Integrins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D011493:Protein Kinase C