慢性炎症与肿瘤恶性转化之间存在内在紧密联系，然而其分子机制并不清楚。申请者前三年工作从CD146在慢性炎症引发恶性转化入手，延伸至血管生成和肿瘤转移，大胆提出血管新生是系慢性炎症和癌症的纽带，CD146是炎症恶性转化的关键节点分子。本项目将延续CD146在炎-癌转化中的重要作用，着重探索CD146与恶性转化和血管生成之间的互动关系；通过鉴定炎-癌恶性转化网络中CD146调控的分子群，阐明CD146活化下游信号通路的分子机制及其表达调控方式；通过对CD146相关受体、配体的鉴定，揭示CD146调控恶性转化及血管新生的分子机制；结合CD146“肿瘤特异性构象”的结构解析，为CD146的作用机制提供结构生物学基础；为深入理解慢性炎症向癌症转化的过程提供新机制，为靶向治疗慢性炎症及肿瘤提供新策略。

It has been well recognized that there is a close relationship between chronic non-resolving inflammation and malignant transformation. However, the molecular mechanism of this process is not clear. In the past three years, we have been focusing on cancer-related inflammation, angiogenesis and metastasis. Our study provided important evidence that CD146, as a node molecule, links chronic non-resolving inflammation and malignant transformation. In this project, we will continue to explore the molecular mechanism of CD146 in chronic non-resolving inflammation and malignant transformation. We will identify CD146 regulated network to clarify the molecular mechanisms of CD146 in the activation of downstream signaling pathways as well as its regulatory mechanisms. We will identify novel receptor or ligand of CD146 to uncover the mechanism of malignant transformation and angiogenesis. We will also resolve the 3-D structures of CD146 to better understand the structural basis of ‘tumor-specific conformation’ of CD146. Our study will not only provide novel molecular mechanism of CD146 in the cancer-related inflammation and malignant transformation, but also provide a new strategy for targeted therapy of chronic inflammation and cancer.