ZnT7 RNAi favors RafGOFscrib−/−-induced tumor growth and invasion in Drosophila through JNK signaling pathway

The disruption of zinc homeostasis has been identified in patients suffering from various cancers, but a causative relationship has not yet been established. Drosophila melanogaster has become a powerful model to study cancer biology. Here using a Drosophila model of malignant tumor RafGOFscrib−/−, we observed that the tumor growth, invasion and migration were enhanced by silencing dZnT7, a zinc transporter localized on the Golgi apparatus. Further study indicated that the zinc deficiency in Golgi of dZnT7 RNAi resulted in ER stress which could activate the c-Jun-N-terminal Kinase (JNK) signaling and this process is mediated by Atg9. Lastly, we demonstrated that the exacerbation of dZnT7 RNAi on tumor was promoted by JNK signaling-dependent cell autonomous and non-autonomous autophagy. These findings suggest that zinc homeostasis in secretory compartments may provide a new therapeutic target for tumor treatment.