Ephrins function as ligands for Eph receptors in many physiological processes, including development of the nervous system. But they also have receptor-like activity themselves. On p. 2179, Ryuichi Sakai and colleagues reveal that this type of `reverse signalling' by ephrin-B1 promotes the invasive properties of cancer cells by regulating the secretion of matrix metalloproteinase 8 (MMP-8). Ephrin-B1, a transmembrane protein, is often overexpressed in highly invasive tumours. The authors show that binding of the Eph receptor B2 (EphB2) to ephrin-B1 expressed by pancreatic cancer cells promotes their secretion of MMP-8. This reverse signalling activity requires the intracellular C-terminus of ephrin-B1 and involves the activation of Arf1 GTPase, a regulator of membrane trafficking. Furthermore, report the authors, the promotion of pancreatic tumour cell invasion in vivo by ephrin-B1 also requires an intact C-terminus. Thus, they propose, the C-terminus of ephrin-B1 regulates the invasive potential of cancer cells by stimulating the secretion of MMP-8, which promotes extracellular matrix degradation and, consequently, invasion.