JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration.
Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of beta1 and beta3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype.
Mandicourt
Guillaume
G
Department of Pathology and Immunology, the University Medical Center, CH 1211 Geneva 4, Switzerland.
Iden
Sandra
S
Ebnet
Klaus
K
Aurrand-Lions
Michel
M
Imhof
Beat A
BA
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D007136:Immunoglobulins / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D019108:Tight Junctions / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019012:Integrin beta1; D016023:Integrins; C486723:Jam3 protein, mouse; D008565:Membrane Proteins