ZnT7 RNAi favors RafGOFscrib-/--induced tumor growth and invasion in Drosophila through JNK signaling pathway.
Tian WeiXiaowen JiYan GaoXiaomei ZhuGuiran XiaoPublished in: Oncogene (2021)
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.
Keyphrases
- signaling pathway
- cell death
- induced apoptosis
- oxide nanoparticles
- end stage renal disease
- pi k akt
- drosophila melanogaster
- newly diagnosed
- endoplasmic reticulum stress
- squamous cell carcinoma
- oxidative stress
- chronic kidney disease
- epithelial mesenchymal transition
- cell therapy
- mesenchymal stem cells
- prognostic factors
- tyrosine kinase
- papillary thyroid
- endoplasmic reticulum
- squamous cell
- intensive care unit
- patient reported
- childhood cancer