The Regulation Mechanism Of β-catenin

The development and progression of cancer is a multigene, multifactor and multistage biological phenomenon. The discovery of oncogenes and tumor suppressor genes, and the research of signal transduction pathway yield profound insights into the mechanisms of carcinogenesis. The oncogene products, in most instances, have been shown to present as a normal part of cellular signal transduction pathways. These products include growth factors, receptors for growth factors, G-protein, G-protein coupled receptors, cytoplasmic kinases and nuclear transcription factors, etc., which play essential roles in normal cellular functions.Cancer causation is a merging result of environmental carcinogen factors and genetic factors. The carcinogenic process induced by carcinogens, in fact, is to lead cellular proliferation, differentiation and apoptosis out of control. These processes, whereas rely on cellular signal transduction. Therefore, the research of signal transduction pathway has become a focus of current molecular biological and development biological studies and cancer research. Meanwhile, these individual fields are providing good support for each other. Wnt pathway is just a perfect example of such multidisciplinary research.Wnt pathway is a highly conserved signal transduction pathway. Its members have a high level of cross-species homology, from fruit fly to mammal. In classical model of Wnt pathway, association of extracellular protein Wnt with its receptor (Frizzled/LRP) at the cell surface triggers the biochemical cascade of events of Wnt pathway. Through this pathway, cytoplasmic protein Dsh is activated upon phosphorylation, which then inhibits β-catenin's phosphorylation by GSK3β/APC/Axin complex. The cytoplasmic unphosphorylated β-catenin is not degraded by the ubiquitin system, allowing translocation into the nucleus where it forms a complex with transcription factor LEF/TCF, activating Wnt-response genes. Many downstream genes of Wnt pathway participate in cellular proliferation and apoptosis, such as c-myc and cylinD1. Wnt signalling pathway not only plays a crucial role in embryogenesis, but also is closely associated with the development and progression of cancers.The regulation of β-catenin's stability and activity is one of the crucial events of Wnt pathway due to its important role. With the relationship research between Wnt pathway and...