Development of a Whole Organism Platform for Phenotype-Based Analysis of IGF1R-PI3K-Akt-Tor Action

作者：Liu, Chengdong; Dai, Wei; Bai, Yan; Chi, Changfeng; Xin, Yi; He, Gen; Mai, Kangsen; Duan, Cunming^*

来源：Scientific Reports, 2017, 7(1): 1994.

DOI：10.1038/s41598-017-01687-3

• PHOSPHATIDYLINOSITOL 3-KINASE
• GENE-EXPRESSION
• CYCLIN D1
• GROWTH
• INSULIN
• ZEBRAFISH
• MTOR
• BINDING
• CANCER
• ACID

Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time. This platform is well suited for high-throughput assays and real-time cell cycle analysis. Using this platform, the dynamics of epithelial cell proliferation in response to low [Ca2+] stress and the distinct roles of Torc1 and Torc2 were elucidated. The availability of Tg(igfbp5a:GFP) line provides a whole organism platform for phenotype-based discovery of novel players and inhibitors in the IIS-PI3K-Akt-Tor signaling pathway.

• 出版日期2017-5-17
• 单位浙江海洋大学; 中国海洋大学