SCF家族E3泛素酶FBXL7在胰腺癌侵袭转移中的作用及机制研究

As the one of the most leading cause of death by cancer, pancreatic cancer has a less than 5% of the 5 year survival rate. Early metastasis of pancreatic cancer leads to high mortality. Unveiling the mechanism of cancer metastasis will contribute to both the basic theroy of cancer and also have clinical application potential. SCF E3 ubiquitin ligase family control abundant protein degradation through the proteasome system, and play important roles in tumorgenesis and progression. However, the data are scare in pancreatic cancer metastasis. By screen, we have found FBXL7 was expecially downregulated in the meatstatic pancreatic cancer, further studies revealed that FBXL7 may promete cancer invasion and metastasis, through regulation of EMT. In this study, we want to look into the detailed molecule mechanisms how FBXL7 regulates pancreatec cancer cell EMT and invasion, and the relavance of FBXL7 expression in the cancer dignosis and prognosis. Our study will fully demostrated the activity and function of FBXL7 from basic research to clincal study, and will provide potential target for pancreatic cancer therapy.

胰腺癌作为预后最差的肿瘤之一，其5年生存率低于5%，严重威胁着人类健康。肿瘤的早期转移是其高致死率的主要原因，对胰腺癌转移的机制进行研究具有基础理论价值和临床应用前景。SCF家族E3泛素酶参与多种蛋白的泛素化降解调控，在肿瘤的发生发展中也发挥重要作用，然而在胰腺癌转移中的研究还不全面。通过分析多中心转移性胰腺癌数据，我们发现了SCF家族分子FBXL7在转移性胰腺癌中低表达，且同EMT标记E-cadherin正相关。本课题拟探讨FBXL7通过调控EMT促进肿瘤转移的详细分子机制，并探讨胰腺癌中FBXL7下调的机制，同时观察FBXL7同临床病人预后之间的关联。本研究有助于更深刻理解胰腺癌复杂的调控网络，并为临床胰腺癌的诊断预后提供依据，同时可能也为临床治疗提供潜在靶点。