新抑癌基因NDRG2在甲状腺癌上皮间质转化中的调控作用

Recurrence and metastasis is the leading cause of death in patients with thyroid cancer, epithelial mesenchymal transition (EMT) is an important mechanism for cancer cell invasion and migration, and to clarify the key regulatory molecules in thyroid cancer in the EMT process is of great significance. NDRG2 gene was first found and cloned in the Department of biochemistry of our University, and it is a new cancer suppress gene. our previous research showed that: low expression levels of both NDRG2 and Na+/K+-ATPase in thyroid cancer tissues; NDRG2 protein can bind to and stabilize the Na+/K+-ATPase protein. Na+/K+-ATPase reported is one of TGF-β down-regulated target molecules and involved in the EMT, intercellular adhesion, and intercellular tight junctions. These studies suggest that NDRG2 may regulate Na+/K+-ATPase in thyroid cancer, and involved the thyroid cancer EMT, but the detailed mechanism needs to be elucidated. This project intends to comprehensive utilization of molecular biology, cell biology, small animal imaging methods, and tissues，from in vitro, in vivo, and clinical specimen three different levels to observe the effects of NDRG2 in thyroid cancer EMT and cancer invasion and metastasis. Provide new understanding of mechanism in thyroid cancer recurrence and metastasis and new ideas for thyroid cancer diagnosis and treatment.

复发和转移是甲状腺癌患者死亡的主要原因，上皮间质转化（EMT）是癌细胞获得侵袭和迁移能力的重要机制，阐明甲状腺癌EMT过程中的关键调控分子意义重大。NDRG2是我校生化教研室最先发现并克隆的基因，是一个新抑癌基因。我们在前期实验中发现：NDRG2和Na+/K+-ATPase在甲状腺癌组织的表达水平均很低；NDRG2可以结合并稳定Na+/K+-ATPase。据文献报道Na+/K+-ATPase是TGF-β下调靶分子，调节上皮细胞EMT、细胞间黏附和细胞紧密连接。上述研究提示NDRG2可能通过调节Na+/K+-ATPase参与甲状腺癌EMT，但详细的作用机制有待深入研究。本课题拟综合利用分子生物学、细胞生物学和小动物活体成像等方法和临床标本，在体外、体内、临床病例水平观察NDRG2对甲状腺癌EMT和侵袭、转移的影响，为甲状腺癌复发和转移机制提出新认识，为甲状腺癌诊断和治疗提供新思路。

复发和转移是甲状腺癌患者死亡的主要原因，上皮间质转化（EMT）是癌细胞 获得侵袭和迁移能力的重要机制，阐明甲状腺癌 EMT 过程中的关键调控分子意义重大。NDRG2 是我校生化教研室最先发现并克隆的基因，是一个新抑癌基因。我们在前期实验中发现： NDRG2 和 Na+/K+-ATPase 在甲状腺癌组织的表达水平均很低；NDRG2 可以结合并稳定 Na+/K+-ATPase。据文献报道 Na+/K+-ATPase 是 TGF-β 下调靶分子，调节上皮细胞 EMT、细 胞间黏附和细胞紧密连接。上述研究提示 NDRG2 可能通过调节 Na+/K+-ATPase 参与甲状腺癌 EMT，但详细的作用机制有待深入研究。本课题拟综合利用分子生物学、细胞生物学和小动 物活体成像等方法和临床标本，在体外、体内、临床病例水平观察 NDRG2 对甲状腺癌 EMT 和 侵袭、转移的影响，为甲状腺癌复发和转移机制提出新认识，为甲状腺癌诊断和治疗提供新 思路。