Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity

Abstract Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect. We also demonstrated that netrin-1 upregulated YAP expression via its transmembrane receptor neogenin. Furthermore, our in vitro and in vivo results showed that the effect of netrin-1 on GC cells migration and invasion abilities was regulated by YAP. Collectively, our results defined netrin-1 as a positive regulator of malignant tumor metastasis in GC by activating the YAP signaling, with potential implications for new approaches to GC therapy.