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PMID:17099249

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Citation

Mandicourt, G, Iden, S, Ebnet, K, Aurrand-Lions, M and Imhof, BA (2007) JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration. J. Biol. Chem. 282:1830-7

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M605666200

Keywords

Amino Acid Sequence; Animals; Antigens, CD29/metabolism; CHO Cells; Cell Adhesion; Cell Adhesion Molecules/physiology; Cell Line, Tumor; Cell Movement; Cricetinae; Cricetulus; Gene Expression Regulation; Immunoglobulins/physiology; Integrins/metabolism; Membrane Proteins/physiology; Mice; Molecular Sequence Data; Sequence Homology, Amino Acid; Tight Junctions/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ITB3

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1933825

P

Seeded From UniProt

complete

MOUSE:ITB1

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1933825

P

Seeded From UniProt

complete

MOUSE:JAM3

acts_upstream_of_or_within

GO:0030010: establishment of cell polarity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAM3

acts_upstream_of_or_within

GO:0016477: cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAM3

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:JAM3

acts_upstream_of_or_within

GO:0007160: cell-matrix adhesion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96610
MGI:MGI:96612

P

Seeded From UniProt

complete

MOUSE:JAM3

located_in

GO:0005911: cell-cell junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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