骨肉瘤干细胞外泌体蛋白Pontin52通过Wnt/β-catenin信号通路调控骨肉瘤侵袭转移的分子机制研究

骨肉瘤干细胞是骨肉瘤复发、转移的根源，外泌体介导的细胞通讯在骨肉瘤干细胞与微环境动态平衡中发挥着重要的作用，干预外泌体的生成、释放、转运及其信号通路传导有可能成为新的骨肉瘤治疗手段。项目组前期研究发现与骨肉瘤非干性亚群细胞外泌体相比，Wnt/β-catenin信号通路中的Pontin52在骨肉瘤干细胞外泌体中表达显著升高，其表达水平影响骨肉瘤细胞的侵袭迁移。项目组拟在前期研究的基础上，深入研究骨肉瘤干细胞外泌体及Pontin52对骨肉瘤干细胞转移前微环境影响，探索Pontin52在骨肉瘤干细胞自我更新和分化中的作用，阐明骨肉瘤干细胞外泌体及Pontin52在骨肉瘤生物学行为中的作用及影响机制，挖掘Wnt/β-catenin等分子信号网络中与Pontin52相互作用的的关键信号分子，揭示这些关键分子发挥效应影响骨肉瘤生物学行为尤其是侵袭转移的作用机制，为骨肉瘤的诊治提供新的思路。

Osteosarcoma stem cells are the major cause of osteosarcoma recurrence and metastasis. Exosome-mediated cell communication plays an important role in the dynamic balance of osteosarcoma stem cells and microenvironment. Blocking the occurrence, release, transport and signaling pathways of exosomes is expected to become a new treatment strategy for osteosarcoma. Our team found that compared with non-stem subpopulation cells of osteosarcoma, the expression level of Pontin52 in Wnt/β-catenin signaling pathway was significantly increased in osteosarcoma stem cell exosomes, and Pontin52 expression level affected the invasion and migration of osteosarcoma cells. On the basis of previous research, our team intend to study the effect of exosomes derived from osteosarcoma stem cells and Pontin52 in the microenvironment associated with metastasis, and explore the function of Pontin52 on self-renewal and differentiation. Our team plan to elucidate the role of exosomes derived from osteosarcoma stem cells and Pontin52 in the process of invasion and metastasis，and investigate key signaling molecules that interact with Pontin52 in signaling networks such as Wnt / β-catenin pathway to reveal the effects of these key molecules. These work would provide new insight for the diagnosis and treatment of osteosarcoma.