Zinc dyshomeostasis in secretory compartments promotes tumor growth and invasion via cell autonomous and non-autonomous autophagy

Abstract

Many zinc transporters have been found to play important roles in human cancers, but the detailed regulatory mechanism have yet to be well identified. Recently, utilizing Drosophila tumor models, we showed that ZnT86D/dZnT7, a zinc transporter localized on the Golgi apparatus, functions as a negative regulator during tumorigenesis. ZnT86D/dZnT7 RNAi results in zinc dys-homeostasis in secretory compartments which leads to ER stress and activates bsk/JNK signaling. The activation of bsk/JNK signaling in ZnT86D/dZnT7 RNAi induces cell autonomous and non-autonomous macroautophagy/autophagy through Atg9. Further, ZnT86D/dZnT7 RNAi enhances tumor growth and invasion via autophagy. These data demonstrate the molecular mechanisms of how ZnT86D/ZnT7 regulates tumor growth and invasion in vivo.

Keywords

• autophagy
• drosophila
• jnk signaling
• secretory compartments
• zinc
• znt7