| Description |
Wnt signaling pathway is an important and highly conserved signaling pathway from nematode, fruit flies, Xenopus to mammalian cells. It is primarily involved in a variety of biological processes, such as cell growth and division, early embryonic development, tissue homeostasis maintenance, stem cell renewal, and tumor occurrence and development. The Wnt gene encodes a large class of glycoproteins secreted outside the cell, of which there are 19 in the human genome. With many Wnt family members, dozens of receptor proteins or co-receptors interacting with Wnt ligands, and downstream signaling factors are even more complex. Decades of research have shown that continuous uncontrolled activation of the classic Wnt pathway with β-catenin as the core effector protein is an important condition for the occurrence of many cancers, including lung cancer, liver cancer and almost all colon and rectal cancer, as well as a key factor for tumor metastasis and cancer progression. Wnt signaling receptor protein complexes, degradation complexes, and endonuclear transcription complexes are important cancer drug targets. At present, many classical inhibitors of the Wnt pathway have entered human clinical trials. In order to further understand the regulatory mechanisms of stem cells and provide a reliable molecular structural basis for the development of anticancer drugs and regenerative medicine, we must clarify how classical Wnt signals are recognized and transmitted, and what the specific molecular mechanisms of β-catenin accumulation and degradation are. There is also a range of core scientific questions, such as how the endonuclear transcription complexes activate transcription of target genes and lead to the development of tumors. This project will combine crystallography technology, cryo-EM technology and biochemical assays to analyze the spatial structure of Wnt transmembrane signal transduction in the classical Wnt pathway, the key protein complex of signal response and transcription regulation in the cytoplasm, and reveal the molecular mechanism of Wnt signal recognition, transmission and activation. And provide a reliable structural basis for design of new therapeutic drugs in cancer. |
