School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230009, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, China.
Oncogene. 2021 Mar;40(12):2217-2229. doi: 10.1038/s41388-021-01703-x. Epub 2021 Mar 1.
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 Rafscrib, 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.
锌稳态的破坏已在患有各种癌症的患者中得到证实，但尚未建立因果关系。果蝇已成为研究癌症生物学的强大模型。在这里，我们使用恶性肿瘤 Rafscrib 的果蝇模型观察到，通过沉默定位于高尔基体的锌转运蛋白 dZnT7，肿瘤生长、侵袭和迁移增强。进一步的研究表明，dZnT7 RNAi 导致高尔基体中的锌缺乏会引发内质网应激，从而激活 c-Jun-N-末端激酶 (JNK) 信号通路，这个过程是由 Atg9 介导的。最后，我们证明了 JNK 信号依赖性细胞自主和非自主自噬促进了 dZnT7 RNAi 对肿瘤的恶化。这些发现表明，分泌隔室中的锌稳态可能为肿瘤治疗提供新的治疗靶点。
