Aziz Faisal, Khan Imran, Shukla Shruti, Dey Debasish Kumar, Yan Qiu, Chakraborty Abhijit, Yoshitomi Hisae, Hwang Seung-Kyu, Sonwal Sonam, Lee Hoomin, Haldorai Yuvaraj, Xiao Jianbo, Huh Yun Suk, Bajpai Vivek K, Han Young-Kyu
The Hormel Institute-University of Minnesota, Austin, MN 55912, USA; Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian 116044, PR China.
The Hormel Institute-University of Minnesota, Austin, MN 55912, USA.
Pharmacol Ther. 2022 Apr;232:107994. doi: 10.1016/j.pharmthera.2021.107994. Epub 2021 Sep 24.
Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, gastric ulcer and gastric carcinoma. H. pylori cytotoxin associated antigen A (CagA) plays a crucial role in the development of gastric cancer. Gastric cancer is associated with glycosylation alterations in glycoproteins and glycolipids on the cell surface. H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer through post-translation modification of fucosylation to develop gastric cancer. The involvement of a variety of sugar antigens in the progression and development of gastric cancer has been investigated, including type II blood group antigens. Lewis Y (LeY) is overexpressed on the tumor cell surface either as a glycoprotein or glycolipid. LeY is a difucosylated oligosaccharide, which is catalyzed by fucosyltransferases such as FUT4 (α1,3). FUT4/LeY overexpression may serve as potential correlative biomarkers for the prognosis of gastric cancer. We discuss the various aspects of H. pylori in relation to fucosyltransferases (FUT1-FUT9) and its fucosylated Lewis antigens (LeY, LeX, LeA, and LeB) and gastric cancer. In this review, we summarize the carcinogenic effect of H. pylori CagA in association with Le and its synthesis enzyme FUT4 in the development of gastric cancer as well as discuss its importance in the prognosis and its inhibition by combination therapy of anti-Le antibody and celecoxib through MAPK signaling pathway preventing gastric carcinogenesis.
幽门螺杆菌（H. pylori）是慢性胃炎、胃溃疡和胃癌的主要致病因素。幽门螺杆菌细胞毒素相关抗原A（CagA）在胃癌的发生发展中起关键作用。胃癌与细胞表面糖蛋白和糖脂的糖基化改变有关。幽门螺杆菌细胞毒素相关抗原A（CagA）通过岩藻糖基化的翻译后修饰在胃癌进展中发挥重要作用，从而引发胃癌。人们已经研究了多种糖抗原在胃癌进展和发展中的作用，包括II型血型抗原。Lewis Y（LeY）在肿瘤细胞表面以糖蛋白或糖脂的形式过度表达。LeY是一种二岩藻糖基化寡糖，由岩藻糖基转移酶如FUT4（α1,3）催化产生。FUT4/LeY的过度表达可能作为胃癌预后的潜在相关生物标志物。我们讨论了幽门螺杆菌与岩藻糖基转移酶（FUT1-FUT9）及其岩藻糖基化的Lewis抗原（LeY、LeX、LeA和LeB）以及胃癌相关的各个方面。在这篇综述中，我们总结了幽门螺杆菌CagA与Le及其合成酶FUT4在胃癌发生中的致癌作用，并讨论了其在预后中的重要性以及通过抗Le抗体和塞来昔布联合治疗通过MAPK信号通路预防胃癌发生的抑制作用。
