Freire de Melo F, Marques HS, Rocha Pinheiro SL, Lemos FFB, Silva Luz M, Nayara Teixeira K, Souza CL, Oliveira MV. Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis. World J Clin Oncol 2022; 13(11): 866-879 [PMID: 36483973 DOI: 10.5306/wjco.v13.i11.866]
Corresponding Author of This Article
Fabrício Freire de Melo, PhD, Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Estrada do Bem Querer, 3293-3391 - Candeias, Vitória da Conquista 45029-094, Brazil. freiremeloufba@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Nov 24, 2022; 13(11): 866-879 Published online Nov 24, 2022. doi: 10.5306/wjco.v13.i11.866
Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis
Fabrício Freire de Melo, Hanna Santos Marques, Samuel Luca Rocha Pinheiro, Fabian Fellipe Bueno Lemos, Marcel Silva Luz, Kádima Nayara Teixeira, Cláudio Lima Souza, Márcio Vasconcelos Oliveira
Fabrício Freire de Melo, Samuel Luca Rocha Pinheiro, Fabian Fellipe Bueno Lemos, Marcel Silva Luz, Cláudio Lima Souza, Márcio Vasconcelos Oliveira, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Brazil
Hanna Santos Marques, Campus Vitória da Conquista, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista 45029-094, Brazil
Kádima Nayara Teixeira, Campus Toledo, Universidade Federal do Paraná, Toledo 85919899, Brazil
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version; all authors agree to be accountable for all aspects of the work in ensuring that questions that are related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Supported byNational Council for Scientific and Technological Development, CNPq Brazil.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrício Freire de Melo, PhD, Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Estrada do Bem Querer, 3293-3391 - Candeias, Vitória da Conquista 45029-094, Brazil. freiremeloufba@gmail.com
Received: August 6, 2022 Peer-review started: August 6, 2022 First decision: September 5, 2022 Revised: September 20, 2022 Accepted: October 11, 2022 Article in press: October 11, 2022 Published online: November 24, 2022
Abstract
Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world’s population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori, and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a “hit-and-run” carcinogenic mechanism. Therefore, this review aims to describe H. pylori- and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.
Core tip: CagA is a translocated effector protein that induces morphofunctional modifications in gastric epithelial cells and persistent chronic gastric inflammation. Upon translocation, the bacterial oncoprotein acts as a promiscuous scaffold or hub protein, which is capable of disrupting multiple host signaling pathways, thereby inducing precancerous cellular alterations. This review aims to describe Helicobacter pylori- and CagA-related oncogenic mechanisms, as well as to discuss the novelties and perspectives in this field.
