Eph是受体酪氨酸激酶最大的亚家族，参与了多种重要的生物学事件，包括胚胎发育和肿瘤发生等，但是在甲状腺癌中的研究尚属空白。我们的前期研究揭示，在配对的甲状腺癌临床样本中，肿瘤组织中的EphB3的mRNA和蛋白水平显著升高，提示EphB3可能在甲状腺癌发生发展中具有重要作用。在甲状腺癌细胞中过表达EphB3或用其配体ephrinB1刺激，均能促进细胞迁移和裸鼠体内的肿瘤转移，而将EphB3 knockdown则抑制了细胞迁移和肿瘤转移。这可能与EphB3对细胞骨架和胞外基质粘附，以及Rho 家族成员的活性影响有关。在本项目中，我们计划深入研究EphB3在甲状腺癌中的作用，尤其是在肿瘤转移过程中与之相互作用的蛋白及信号转导途径，揭示EphB3在甲状腺癌中相关的分子调控机制。本项研究不仅有助于扩展我们对Eph家族在肿瘤中的作用及机制的认识，而且也为甲状腺癌提供潜在的分子诊断标志物和治疗靶点。

As the largest subfamily of Receptor Tyrosine Kinases, Ephs participate in many important biological events, including embryogenesis and tumorigenesis.However, their functions in thyroid cancer remain unknown. In the preliminary study, we have found that in paired thyroid cancer samples, the expression of EphB3 in cancerous tissues was increased compared to the matched normal tissues at both mRNA level and protein level. EphB3 overexpression as well as stimulation by its ligand ephrin-B1 promoted cell migration and metastasis of thyroid cancer cells in nude mice, while knockdown of EphB3 exhibited the inhibitory effect. The effect on thyroid cancer cell migration and metastasis by EphB3 may be attributed to its influences on cell skeleton,cell adhesion to the extracellular matrix and the activities of Rho family members. In this program, we plan to investigate the role of EphB3 in thyroid cancer, especially the proteins interacting with EphB3 and the signaling transduction of EphB3 during the process of thyroid cancer metastasis. In addition, we will explore the regulatory mechanisms of EphB3 in thyroid cancer. This study will not only enhance our knowledge of the role and signaling transduction of Eph family in cancer, but also provide potential diagnostic markers and therapeutic targets for thyroid cancer.