PCDHB2促进乳腺癌骨转移的功能和机制研究

Bone is the primary metastatic targeted organ in breast cancer. Due to lack of effective preventive and therapeutic target clinically, bone metastasis is the leading cause of death in breast cancer patients. Our preliminary work found that protocadherin beta 2 (PCDHB2) was highly expressed in several subtypes of breast cancer tissue with bone metastasis, which predicted high risk of bone metastasis in breast cancer patients. Furthermore, our results further revealed that PCDHB2 promoted bone metastasis of breast cancer via both activating Wnt/β-catenin and TGF-β signal pathways. However, the molecular mechanism by which PCDHB2 simultaneously activates Wnt/β-catenin and TGF-β signaling pathways remains not elucidated yet, which is an urgent scientific issue. Based on our previous research results, we will utilize the techniques of cell biology, molecular biology and animal experiments to determine the biological functions of PCDHB2 in bone metastasis process of different subtypes of breast cancer, as well as clarify the molecular mechanism by which PCDHB2 contributes to simultaneous activation of Wnt/β-catenin and TGF-β signaling pathways. The implementation of this project will reinforce our understanding for bone metastasis of breast cancer, which will not only provide important theoretical evidence to screen drug-target against bone metastasis of breast cancer, but also facilitate the exploitation of novel targeted medicine and design of diagnostic and therapeutic strategy.

骨是乳腺癌转移的主要靶器官，但目前临床上缺乏有效的早期诊治手段，因此骨转移成为乳腺癌患者死亡的重要原因。申请人前期工作发现原钙粘附蛋白β2（PCDHB2）在多个亚型骨转移乳腺癌组织中高表达，且其高表达在不同亚型乳腺癌患者中均能够预示更高的骨转移风险。进一步实验发现，PCDHB2通过激活Wnt/β-catenin和TGF-β双信号，从而促进乳腺癌骨转移。然而，PCDHB2如何激活Wnt/β-catenin和TGF-β信号通路尚不清楚，是亟待回答的科学问题。本课题在前期研究工作基础上，利用细胞生物学、分子生物学和动物实验等技术，明确PCDHB2在不同亚型乳腺癌骨转移中的生物学功能，并揭示其在激活Wnt/β-catenin和TGF-β促进乳腺癌骨转移的分子机制。本项目的顺利实施，将增强我们对乳腺癌骨转移的理解，从而为后续临床筛选药物靶点提供重要的理论依据，并有望指导新型靶向药物及诊治方案的研发。

骨是乳腺癌转移的主要靶器官，但目前临床上缺乏有效的早期诊治手段，因此骨转移成为乳腺癌患者死亡的重要原因。申请人前期工作发现原钙粘附蛋白β2（PCDHB2）在多个亚型骨转移乳腺癌组织中高表达，且其高表达在不同亚型乳腺癌患者中均能够预示更高的骨转移风险。进一步实验发现，PCDHB2通过激活Wnt/β-catenin和TGF-β双信号，从而促进乳腺癌骨转移。然而，PCDHB2如何激活Wnt/β-catenin和TGF-β信号通路尚不清楚，是亟待回答的科学问题。本课题在前期研究工作基础上，利用细胞生物学、分子生物学和动物实验等技术，明确PCDHB2在不同亚型乳腺癌骨转移中的生物学功能，并揭示其在激活Wnt/β-catenin和TGF-β促进乳腺癌骨转移的分子机制。本项目的顺利实施，将增强我们对乳腺癌骨转移的理解，从而为后续临床筛选药物靶点提供重要的理论依据，并有望指导新型靶向药物及诊治方案的研发。