Structural basis for carcinogenesis and cancer metastasis by oncogene products

为了阐明肿瘤发生、转移和抗肿瘤免疫反应的机制，将利用x射线晶体学测定参与者、癌蛋白和抗癌蛋白的原子结构。基于这些结构，新的抗癌药物将被开发出来，从而实现有效的癌症治疗。对于癌变，我们关注TGF-β信号，在该信号下，许多转录调节分子相互作用，进行细胞发育信号转导。对于癌症的转移和侵袭，我们关注的是负责细胞骨架重组和质膜供应以及胞吐作用的蛋白质。对于先天免疫反应，我们主要关注toll样受体（TLR）及其内源性配体，以及主要在TLR控制下激活促炎细胞因子和γ-干扰素转录的IRF转录调节因子。

To elucidate the mechanism of carcinogenesis, cancer metastasis and anti-tumor immune reaction, atomic structures of the player, the oncoproteins and anti-oncoproteins will be determined by X-ray crystallography. Based on the structures, new anti-cancer drug will be developed to achieve an efficient cancer treatment. For carcinogenesis, we focus on TGF-β signal under which many transcription regulatory molecules interplay for cellular development signal transduction. For cancer metastasis and invasion, we focus on proteins responsible for cytoskeleton reorganization and plasma membrane supply coupled with exocytosis. For innate immune reaction, we focus on Toll-like receptor (TLR) and its endogenous ligands, and on IRF transcriptional regulators acting mainly under the control of TLR to activate the transcription of proinflammatory cytokines and γ-interferon.