Liver Cancer and the Role of Protein Hyper-Fucosylation

描述（由申请方提供）：这是一份重新提交的提案，旨在了解与原发性人肝细胞癌（HCC）相关的糖蛋白高岩藻糖基化的性质。与健康个体相比，HCC患者的循环中含有丰富的N-聚糖核心处具有岩藻糖基化的糖蛋白。关于为什么这种修饰如此升高，如果它与蛋白质功能和/或在疾病中起作用，则知之甚少。甚至不确定是否是癌细胞产生岩藻糖基化糖型。在岩藻糖基化和非岩藻糖基化糖型的比较研究中，这种修改后的应用将系统地确定哪些细胞正在产生三种“哨兵”高岩藻糖基化糖蛋白，以及岩藻糖基化的功能后果。蛋白质血红素结合蛋白、激肽原和GP 73，每一个都被确定为在岩藻糖基化糖型中与HCC相关，被选择来代表不同的类别。在此过程中，还将测试岩藻糖基化在指导肝细胞糖蛋白分选中发挥作用的重要假设。因此，这项工作的结果旨在回答为什么岩藻糖基化似乎是HCC的一个共同特征的基本问题，并有助于开发早期检测和可能的治疗干预措施。公共卫生相关性：通过在诊断为肝癌的人的血液中检测到的蛋白质含有糖，岩藻糖。了解原因将有助于开发新的诊断方法，并为开发新的治疗方法提供线索。

DESCRIPTION (provided by applicant): This is a re-submission of a proposal to gain an understanding about the nature of the hyper-fucosylation of glycoproteins associated with primary human hepatocellular carcinoma (HCC). Compared to healthy individuals, the circulation of people with HCC contains an abundance of glycoproteins with fucosylation at their N-glycan cores. Little is known about why this modification is so elevated, if it relates to protein function and/or plays a role in disease. There is even uncertainty about whether or not it is the cancer cells that are producing the fucosylated glycoforms. This modified application will systematically determine which cells are producing three "sentinel" hyper-fucosylated glycoproteins, as well as the functional consequences of fucosylation, in comparative studies with fucosylated and unfucosylated glycoforms. The proteins hemopexin, kininogen and GP73, each determined to correlate in the fucosylated glycoform with HCC, are chosen to represent different categories. In doing this, the important hypothesis that fucosylation plays a role in directing the sorting of hepatocytes glycoproteins will also be tested. The results of this work are thus intended to answer the fundamental question as to why fucosylation seems to be a common feature in HCC and help in developing early detection and possibly therapeutic interventions. PUBLIC HEALTH RELEVANCE: By proteins detected in the blood of people with a diagnosis of liver cancer contain the sugar, fucose. Understanding why will help in the development of new diagnostic methods, as well as provide clues for development of new therapies.