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: 7729336
• 负责人: Timothy M Block
• 金额: $ 30.98万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7729336
• 关键词: AFP gene; Appearance; Biological; Biopsy; Blood; Blood Circulation; Categories; Cells; Comparative Study; Development; Diagnosis; Diagnostic Procedure; Disease; Early Diagnosis; Fucose; Glycoproteins; Half-Life; Hemopexin; Hepatocyte; Human; Individual; Kininogens; Liver Cirrhosis; Liver diseases; Malignant neoplasm of liver; Modification; Nature; Patients; Play; Polysaccharides; Primary carcinoma of the liver cells; Proteins; Role; Sentinel; Sorting - Cell Movement; Testing; Therapeutic Intervention; Time; Tissues; Uncertainty; Work; base; cancer cell; novel diagnostics; protein function; public health relevance; sugar

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.

描述（由申请人提供）：这是重新提交的提案，旨在了解与原发性人肝细胞癌（HCC）相关的糖蛋白超岩藻糖基化的性质。与健康个体相比，HCC 患者的循环中含有大量 N-聚糖核心具有岩藻糖基化的糖蛋白。如果这种修饰与蛋白质功能有关和/或在疾病中发挥作用，那么我们对为什么这种修饰如此升高知之甚少。甚至不确定是否是癌细胞产生岩藻糖基化糖型。这种修改后的应用将在岩藻糖基化和非岩藻糖基化糖型的比较研究中系统地确定哪些细胞正在产生三种“前哨”超岩藻糖基化糖蛋白，以及岩藻糖基化的功能后果。血红素结合蛋白、激肽原和 GP73 蛋白均被确定为岩藻糖基化糖型与 HCC 相关，被选择代表不同的类别。在此过程中，岩藻糖基化在指导肝细胞糖蛋白的分类中发挥作用的重要假设也将得到测试。因此，这项工作的结果旨在回答一个基本问题：为什么岩藻糖基化似乎是 HCC 的一个常见特征，并有助于开发早期检测和可能的治疗干预措施。公共健康相关性：在肝癌诊断患者的血液中检测到的蛋白质含有岩藻糖。了解其中的原因将有助于开发新的诊断方法，并为开发新疗法提供线索。