Liver Cancer and the Role of Protein Hyper-Fucosylation

描述(由申请人提供)：这是一项重新提交的提案，目的是了解与原发性人类肝细胞癌(HCC)相关的糖蛋白的高岩藻糖基化的性质。与健康人相比，肝细胞癌患者的血液循环中含有丰富的糖蛋白，其N-糖链核心处有岩藻糖基化。如果它与蛋白质功能有关和/或在疾病中发挥作用，人们对这种修饰为什么会如此升高知之甚少。甚至还不确定是否是癌细胞产生了岩藻糖化糖体。这一改进的应用将在与岩藻糖化和非岩藻糖化糖型的比较研究中，系统地确定哪些细胞产生三种“前哨”超岩藻糖化糖蛋白，以及岩藻糖化的功能后果。血凝素、激肽原和GP73蛋白，每一个都被确定为岩藻糖基化形式与肝细胞癌相关，代表不同的类别。在此过程中，岩藻糖基化在指导肝细胞糖蛋白分选中的作用这一重要假设也将得到检验。因此，这项工作的结果旨在回答为什么岩藻糖基化似乎是肝细胞癌的共同特征这一根本问题，并有助于开发早期发现和可能的治疗干预措施。公共卫生相关性：被诊断为肝癌的人血液中检测到的蛋白质中含有糖、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.