Cleaved JAM-A - connecting cancer and vascular disease?

Breast cancers that overexpress the human epidermal growth factor receptor-2 (HER2) are associated with aggressive disease and poor patient prognosis. Although several highly-effective HER2 targeted therapies have been developed, they are associated with a high incidence of de novo and acquired drug resistance in patients. Therefore there remains an ongoing need to elucidate mechanisms of resistance in order to establish effective treatments in drug-resistant patients. Proteins which operate upstream of, and regulate, HER2 expression are valid pharmacological targets in this setting. In recent years a correlation between the expression of Junctional Adhesion Molecule-A (JAM-A) and HER2 in breast cancers has been reported, in addition to expressional regulation of HER2 by JAM-A. JAM-A is a tight junction protein with important adhesive functions in multiple physiological barriers, but whose overexpression has also been linked with tumor progression in glioblastoma, gastric, lung and nasopharyngeal cancers, as well as an emerging role in cancer stem cell maintenance