JNK信号通路与Wg信号通路的相互作用及机制研究

The JNK and Wnt/Wg signaling are two critical signal transduction pathways in development, which have been conserved from fly to human. The two signal pathways play pivotal roles in cell proliferation, differentiation, migration and apoptosis, while their deregulation have been implicated in many diseases including developmental defects and cancers. However, little is known about whether the two pathways interact with each other to regulate certain physiological processes in development and disease, not to mention the mechanism. We have used Drosophila as a model organism, and showed previously that activated JNK signaling in the eye induced cell death and produced a small eye phenotype. Using this phenotype, we have performed a genetic screen and found that the canonical Wg pathway is required for JNK-mediated cell death. In addition, activated JNK signaling up-regulates the transcription of wg. Based on the previous data, we will further investigate the interaction between the two pathways, find the interaction point, elucidate the mechanism, and examine the role of this interaction in cell death, proliferation, migration and tumor progression. This study not only help us to understand the interaction between different signal pathways in development, improve the current signal pathway network, but also provide novel therapeutic strategies and drug targets for the prevention and cure of diseases like cancer.

JNK信号通路与Wnt/Wg信号通路是发育中的两条重要的信号转导通路，从果蝇到人类高度保守，在细胞增殖、分化、迁移及凋亡等生理过程中起重要作用，其失调与发育缺陷和肿瘤等多种重大疾病的发生与发展密切相关。这两条信号通路在发育和疾病中是否发生交互作用，共同调控某些生理过程，目前所知甚少，其作用机制更不清楚。我们以果蝇为模式动物，在其眼中激活JNK信号通路，可诱导细胞凋亡并产生小眼表型。我们利用此表型对果蝇基因组进行遗传筛选，发现JNK通路介导的细胞凋亡依赖经典的Wg信号通路的参与，而且，JNK通路能调节Wg基因的转录。本项目拟在前期研究基础上，深入研究这两条信号通路的相互作用，确定作用位点，阐明作用机制，诠释其对细胞凋亡、增殖、迁移及肿瘤的调控作用。这项研究有助于我们了解发育中不同信号通路间的相互作用，完善调控发育的信号转导网络，并为癌症等疾病的防治提供新的药物靶点和治疗方案。

JNK、Wg、Hippo信号通路是动物发育中起重要作用的信号转导通路，从果蝇到人类高度保守，调控细胞增殖、迁移及凋亡等过程，其失调与发育缺陷和肿瘤等多种重大疾病的发生发展密切相关。这些信号通路在发育和疾病中是否发生交互作用，共同调控某些生理过程，目前所知甚少，其作用机制更不清楚。我们以果蝇为模式动物，在不同组织中激活JNK信号通路，可诱导细胞凋亡和迁移的发生，并产生相应表型。我们利用上述表型对果蝇基因组进行遗传筛选，发现JNK通路与经典的Wg、Hippo信号通路相互作用，共同调控细胞凋亡和细胞迁移，便参与肿瘤的发生与侵袭。通过本项目的研究，我们探明了这些信号通路互作的方式，发现了新的调控因子，确定了相互作用的位点和机制。本项目的研究不仅有助于我们了解发育中不同信号通路间的相互作用，完善调控发育的信号转导网络，也为癌症等疾病的防治提供了新的药物靶点和治疗方案。