Model of JAM-A signalling in human breast cancer cells. Our working model hypothesizes that, in normal breast cells, a baseline level of JAM-A signalling via AF-6 and PDZ-GEF2 leads to a low level of β1-integrin-mediated cell migration required for crucial normal physiological processes such as wound healing (a). However, in breast cancer cells, overexpression of JAM-A leads to its increased association with PDZ-GEF2 protein and this in turn hyperactivates the GTPase Rap1. We suggest that this culminates in increased β1-integrin-mediated cancer cell migration and leads to increased risk of invasion and metastasis (b). ECM, extracellular matrix; JAM-A, junctional adhesion molecule-A.