Partners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer.

Abstract

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 LeY 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-LeY antibody and celecoxib through MAPK signaling pathway preventing gastric carcinogenesis.

• Authors: Faisal Aziz, Imran Khan, Shruti Shukla, Debasish Kumar Dey, Qiu Yan, Abhijit Chakraborty, Hisae Yoshitomi, Seung-Kyu Hwang, Sonam Sonwal, Hoomin Lee, Yuvaraj Haldorai, Jianbo Xiao, Yun Suk Huh, Vivek K Bajpai, Young-Kyu Han
• Journal: Pharmacology & therapeutics (Pharmacol Ther) Vol. 232 Pg. 107994 (04 2022) ISSN: 1879-016X [Electronic] England
• PMID: 34571111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Lewis Blood Group Antigens
• Lewis Y antigen
• FUT4 protein, human
• Fucosyltransferases

Topics

• Crime
• Fucosyltransferases (metabolism)
• Helicobacter Infections (complications)
• Helicobacter pylori
• Humans
• Lewis Blood Group Antigens (metabolism)
• Stomach Neoplasms (metabolism)