Wnt5a/Ca2+/NFAT与NF-KB信号通路对话维持成釉细胞瘤炎性微环境促进其侵袭的机制

Ameloblastoma (AB) is the most common epithelial odontogenic tumor with aggressive growth, lack of effective treatment and clear pathogenesis.The inflammatory tumor microenvironment is closely with tumor invasiveness. Tumor-associated macrophages (TAM) is an important component in the inflammatory microenvironment of AB, whose subtype differentiation is related to tumor progression and regulated by tumor microenvironment.Wnt5a/Ca2+/NFAT and NF-κB signaling pathway play an important role in the maintenance of inflammatory microenvironment and tumor development.This project will study on the regulatory role of tumor cell on the microenvironment, exploring the crosstalk of Wnt5a/ Ca2+ / NFAT and NF-?B signaling pathway in the regulation of inflammatory microenvironment analysing the intrinsic relationship between inflammatory tumor microenvironment and tumor invasion.We aim to establish a signaling network system between AB and inflammatory microenvironment,discover novel signaling pathway and regulatory target on the basis of internal and external environment change,identify possible targets for blocking tumor metastasis, explore the mechanism of tumorigenesis and seek out new drug targets,provide theoretical and experimental evidence for the reasonable treatment of AB.

成釉细胞瘤（AB）是最常见的上皮性牙源性肿瘤，局部侵袭性生长，由于其发病机制尚不明确，因此缺乏有效的治疗措施。肿瘤炎性微环境和该肿瘤侵袭性关系密切，肿瘤相关巨噬细胞（TAM）是AB炎性微环境的重要成份，其向何种亚型分化和肿瘤进程相关，并受肿瘤微环境调控。Wnt5a/Ca2+/NFAT和NF-κB通路在维护炎性微环境及促进肿瘤生长中起着重要作用。本项目从肿瘤实质对微环境调控的角度入手，探索AB中Wnt5a/ Ca2+/NFAT和NF-κB信号通路crosstalk对肿瘤炎性微环境的调控作用，解析肿瘤炎性微环境和肿瘤侵袭性行为内在联系。建立AB与炎性微环境间信号传递的网络分析系统，通过对细胞内外微环境变化分析，发现新的信号传导通路和调节位点，确定可能的肿瘤转移干扰阻断靶点，阐明该肿瘤发生发展的作用机制，为探索新的药物靶点，设计合理的治疗方案提供理论和实验依据。

成釉细胞瘤（AB）是最常见的上皮性牙源性肿瘤，局部侵袭性生长,由于其发病机制尚不明确,因此缺乏有效的治疗措施。肿瘤炎性微环境和该肿瘤侵袭性关系密切，肿瘤相关巨噬细胞（TAM）是AB炎性微环境的重要成份，其向何种亚型分化和肿瘤进程相关，并受肿瘤微环境调控。Wnt5a/Ca2+/NFAT和NF-κB通路在维护炎性微环境及促进肿瘤生长中起着重要作用。本项目从肿瘤实质对微环境调控的角度入手，探索AB中Wnt5a/ Ca2+/NFAT和NF-ĸB信号通路crosstalk对肿瘤炎性微环境的调控作用，解析肿瘤炎性微环境和肿瘤侵袭性行为的内在联系。建立AB与炎性微环境间信号传递的网络分析系统，通过对细胞内外微环境变化的分析，发现新的信号传导通路和调节位点，确定可能的肿瘤转移干扰阻断靶点，阐明该肿瘤发生发展的作用机制，为探索新的药物靶点，设计合理的治疗方案提供理论和实验依据。