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 Raf(GOF) scrib(-/-), 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.

Automated summary

The disruption of zinc homeostasis in secretory compartments, particularly the Golgi apparatus, has been found to enhance tumor growth, invasion, and migration in a Drosophila model of malignant tumors. This zinc deficiency-induced ER stress activates the JNK signaling pathway mediated by Atg9, ultimately promoting tumor exacerbation through JNK signaling-dependent autophagy. These results suggest a potential new therapeutic target for tumor treatment.