Liver Cancer and the Role of Protein Hyper-Fucosylation

肝癌和蛋白质高岩藻糖基化的作用

• 批准号: 9011170
• 负责人: Timothy M Block
• 金额: $ 0.62万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-19 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9011170
• 关键词: Liver; Cancer; Role; Protein; Hyper

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.

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。

项目成果

Chronic hepatitis B: what should be the goal for new therapies?

• DOI: 10.1016/j.antiviral.2013.01.006
• 发表时间: 2013-04
• 期刊: ANTIVIRAL RESEARCH
• 影响因子: 7.6
• 作者: Block, Timothy M.;Gish, Robert;Guo, Haitao;Mehta, Anand;Cuconati, Andrea;London, W. Thomas;Guo, Ju-Tao
• 通讯作者: Guo, Ju-Tao