The role of junctional adhesion molecule-A in cancer cell migration and morphology

Abstract

The cell adhesion molecule (CAM) family of proteins is a large group of proteins that are typically transmembrane proteins used in the attachment of the cell to another cell or to the extracellular matrix (ECM). Junctional adhesion molecule A (JAM-A) is a member of the CAM family that has recently been identified to have a role in various cancers. Currently there is conflicting data for JAM-A in breast cancer concerning the role of JAM-A in cellular migration. Using the highly metastatic cell line MDA-MB- 231, the aim for this study was to determine JAM-A’s role in the migration of the MDA-MB-231 breast cancer cells and to start to determine the mechanism by which JAM-A may be contributing. Through transfection of the MDA-MB-231 cells with full length JAM-A, cytoplasmic deletion JAM-A (Δ257 JAM-A) and tyrosine to phenylalanine 261 JAM-A (Y-F261 JAM-A), this study shows that full length JAM-A decreased the migration of MDA-MB-231 cells and surprisingly Y-F261JAM-A along with Δ257 JAM-A further decreased migration in transfected cells. Using immunofluorescence it was determined that JAM-A localized at the cell-to-cell adhesions between the transfected MDA-MB-231 cells and contributed to a more epithelial like morphology overall. Also through immunofluorescence, it was shown that transfection with full length JAM-A, Δ257 JAM-A and Y-F261 JAM-A increased the cell-to-cell adhesions. These findings make JAM-A an interesting protein to examine in the migration and metastasis of metastatic breast cancer.