纤毛重构调控Hedgehog信号-自噬效应链对去分化软骨肉瘤恶性进程的影响及机制研究

项目名称： 纤毛重构调控Hedgehog信号-自噬效应链对去分化软骨肉瘤恶性进程的影响及机制研究

项目编号： No.81672652

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 许凯

作者单位： 华中科技大学

项目金额： 25万元

中文摘要： 软骨肉瘤是第二常见的恶性骨肿瘤，其中去分化软骨肉瘤恶性程度高、发展快、缺乏有效的治疗手段，其恶性生物学行为的调控机制尚不明确。初始纤毛作为Hedgehog通路重要的信号传导单元参与调控软骨发育，同时初始纤毛还是重要的细胞感受器介导细胞和微环境之间的联系，有证据显示纤毛缺失与肿瘤的恶性进程密切相关，且参与调控Hedgehog-自噬效应链进而左右细胞命运。申请者在前期研究中发现软骨肉瘤中存在纤毛的低表达，同时伴有Hedgehog通路的异常激活，诱导纤毛重构可伴有自噬上调并影响软骨肉瘤的恶性生物学行为。本项目拟通过探究可调控纤毛与自噬表达对去分化软骨肉瘤Hedgehog通路及肿瘤恶性进程的影响，明确Hedgehog通路参与调控纤毛与自噬交互作用的潜在机制，阐明纤毛影响Hedgehog-自噬效应链在去分化软骨肉瘤恶性进程中的作用，为寻找基于纤毛表达差异的软骨肉瘤治疗新方法提供理论和实验基础。

中文关键词： 骨肿瘤；初始纤毛；Hedgehog-自噬效应链；去分化软骨肉瘤；恶性进程

英文摘要： Chondrosarcoma is the second malignant bone tumor，Dedifferentiated chondrosarcoma is a distinct form of chondrosarcoma where a high-grade sarcoma is found adjacent to a low grade chondrosarcoma. This aggressive tumor is associated with a poor prognosis and its maligment regulation mechanism is still not clear. Primary cilia, an important part of Hedgehog pathway, can regulate cartilage development, but the mechanism of primary cilia on regulating dedifferentiated chondrosarcoma development is not yet clear. Cilia are important sensors and signal transduction units in cells and mediate the connection between cells and microenvironment. Many researches have shown that cilia deficiency had a close link with tumor malignant processes and involved in regulating Hedgehog-autophagy effect chain to determine cells fate. In our previous study, we have found that primary cilia expressed lower in chondrosarcoma with an abnormal activation of Hedgehog signaling compared with normal cartilage. Induction of cilia remodeling could be associated with an increase of autophagosome and influence chondrsarcoma cells malignant biological behaviors. This project aim to explore the effects on Hedgehog pathway to regulate dedifferentiated chondrosarcoma malignant process by regulating cilia and autophagy expression and identify the potential mechanism of Hedgehog pathway involved in cilia and autophagy interaction. To clarify the role of primary cilia affecting Hedgehog-autophagy effect chain in regulating dedifferentiated chondrosarcoma development and malignant process will provide new theoretical basis and experimental basis to find a new treatment of chondrosarcoma based on the different expression of primary cilia.

英文关键词： bone tumor;primary cilia;Hedgehog-autophagy effect chain;dedifferentiated chondrosarcoma;malignant process