The Wnt Signaling Pathway As A Target For High-throughput Drug Screening Cell Model

The name of WNT signaling pathway came from the combination of both mice mamammary tumor gene INT-1 and its homologous gene WINGLESS in Drosophila. This signaling pathway has been identified as one of the key signaling pathways in cancer, regulating cell growth, motility and differentiation. Because of its widespread activation in diverse human tumor diseases, it has gained considerable and growing interest in tumor research over recent years. The aim of this experiment is to establish WNT signaling pathway targeted high-throughput drug screening cell model marked by Green Fluorescence Protein(E-GFP), which can be used in screening on WNT signaling pathway related antitumor and disease drug candidates.WNT signal pathway has been illuminated as a very complicated signaling network, involved in many protein and enzyme interactions . This pathway has been divided into at least three branches, In this research issue, we just aim at the WNT— β -CATENIN-LEF/TCF branch , so called as the canonical WNT pathway. This pathway branch focuses on the WNT-dependent gene transcription and tumor related gene regulation, can regulate the gene activation, playing the most important role in the WNT-related tumorigenesis.The activation of this branch dependent on the inhibition of intracellular protein- enzyme complex forming, such as tumor suppressor gene product APC, AXIN, Casein kinase(CK)1a, 1e, and glycogen synthase kinase(GSK-3β ). Lithium can inhibit the activation of GSK-3β , then inhibit the protein complex-coupled phosphorylation and degradation process, which can result in decrease of the intracellular phosphorylation and degradation level of β -CATENIN, increase of the amount of β-CATENIN which enter into the nucleus, finally regulate the transcription of the target gene under the interactions with so many transcription factors. It...