肝转移是胰腺神经内分泌肿瘤治疗的难点与关键。我们的前期研究证实，胰腺神经内分泌肿瘤是否发生肝转移与肿瘤细胞Raf-1/MEK/ERK通路的开放或关闭密切相关。进一步研究发现，TOPK可能通过与Raf-1/MEK/ERK通路的相互作用参与了胰腺神经内分泌肿瘤肝转移的调节，与Raf-1和ERK位点均存在调节作用，提示TOPK可能是预防和治疗胰腺神经内分泌肿瘤肝转移的治疗靶点。本项目围绕TOPK与Raf-1/MEK/ERK的相互作用展开研究。拟通过对TOPK磷酸化位点的生物信息学分析，筛查、确定TOPK与Raf-1/MEK/ERK相互作用的位点、对激酶活性的影响、对Raf-1/MEK/ERK通路的影响，以及对肿瘤肝转移的影响。我们期望，从分子机制上进一步揭示TOPK、Raf-1/MEK/ERK与胰腺神经内分泌肿瘤肝转移之间的关系，寻找胰腺神经内分泌肿瘤肝转移关键治疗靶点。

The key point and difficulty of the treatment for pancreatic neoroendocrine neoplasm is the liver metastasis. The occurence of the liver metastasis of pancreatic neoroendocrine tumor is closely related to the open or closure of Raf-1/MEK/ERK pathway of tumor cell, which is proved by our previous studies. The progress of research in TOPK (TLAK cell-originated protein kinase) suggests that TOPK may involve the accommodation of the liver metastasis of pancreatic neoroendocrine neoplasm via the interaction with the Raf-1/MEK/ERK pathway. It means TOPK might be a therapuetic target for the liver metastasis of pancreatic neoroendocrine neoplasm.This project is focused on the interaction of TOPK and Raf-1/MEK/ERK pathway. Using bioinformatic analysis for the phosphorylation site of TOPK, we try to screen and identify the interaction site of TOPK and Raf-1/MEK/ERK pathway, as well as the effect of TOPK to the activity of kinase, to the Raf-1/MEK/ERK pathway, and to the liver metastasis of tumor. We expected to explore the relationship between TOPK, Raf-1/MEK/ERK pathway and liver matastasis of pancreatic neoroendocrine neoplasm on the molecular mechanism level, and to seek the key therapuetic targets for pancreatic neoroendocrine neoplasm.