RIP endothelial cells

In order to metastasize, circulating tumour cells must exit the bloodstream by passing through the endothelial barrier. This process of extravasation is poorly understood. Strilic et al. now provide evidence that tumour cells can induce necroptosis of endothelial cells to drive transendothelial migration and metastasis. This is achieved through a mechanism involving the interaction of the amyloid precursor protein (APP) on tumour cells with its receptor, death receptor 6 (DR6) on endothelial cells. Consistent with involvement of a necroptotic signalling pathway, treatment of experimental mouse models of lung metastasis with necrostatin 1, an inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1), decreased endothelial cell death. Exactly how this endothelial cell killing enables tumour cells to colonize a new tumour site should be an exciting area of future research.