中文摘要
肝细胞癌(Hepatocellular carcinoma, HCC)是人类最常见的恶性肿瘤之一,严重威胁我国人民生命健康安全。HCC术后的复发转移是导致其死亡率居高不下的最主要因素。肿瘤的复发转移是一个复杂的、连续的、多分子参与的级联过程。目前已知乙型肝炎病毒的感染,糖基异常化修饰和细胞表面受体的激活都与HCC的复发转移有关。但三者之间关系如何,通过怎样的方式协同参与HCC的复发转移过程仍不清楚。我们拟在前期研究的基础上,以肝癌细胞和组织为研究对象,围绕乙肝相关肝癌中病毒蛋白HBx和N-乙酰氨基葡萄糖转移酶Ⅲ(GnT-III)的调控作用,建立肝癌细胞表面酪氨酸激酶受体B(TrkB)分子N-糖基化修饰参与乙肝相关肝癌转移复发的分子调控和干预机制,为开发针对N-糖基化修饰和TrkB信号通路的肝癌分子靶向治疗研究和药物开发奠定基础。
英文摘要
Hepatocellular carcinoma (Hepatocellular carcinoma HCC) is one of the most common human malignancies, a serious threat to the life and health of our people. Postoperative HCC recurrence and metastasis are the main factors leading to the high mortality rate . Tumor recurrence and metastasis is a complex, multi molecular continuous, participation in the cascade process. Currently known hepatitis B virus infection, activate the glycosylation abnormalities and the cell surface receptors are related to metastasis and recurrence of HCC. But how the relationship between the three, whether mutual cooperation to jointly participate in the HCC recurrence and metastasis is still unclear. We plan on the basis of previous studies, the hepatic cancer cells and tissue as the research object, surrounding the virus HBx protein and N-acetylglucosaminyltransferase III (GnT-III) function, establishment of liver cancer cell surface receptor tyrosine kinase B (TrkB) molecule N- glycosylation participate in HBV related hepatocellular carcinoma metastasis and recurrence molecular regulation and intervention mechanism, and lay the foundation for the development of liver cancer molecular target for N- glycosylation and the activation of TrkB signaling to the treatment of research and drug development.
