Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. May 20, 2015; 5(2): 84-102
Published online May 20, 2015. doi: 10.5493/wjem.v5.i2.84
Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review
Miguel Angel Chiurillo
Miguel Angel Chiurillo, Laboratorio de Genética Molecular “Dr. Yunis-Turbay”, Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Estado Lara, Venezuela
Miguel Angel Chiurillo, Departamento de Patologia Clínica, Universidade Estadual de Campinas, Campinas 13083, São Paulo, Brasil
Author contributions: Chiurillo MA solely contributed to this paper.
Conflict-of-interest: The author has no conflict of interest to declare.
Open-Access: 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/
Correspondence to: Miguel Angel Chiurillo, MD, PhD, Laboratorio de Genética Molecular “Dr. Yunis-Turbay”, Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Estado Lara, Venezuela. mchiurillo@ucla.edu.ve
Telephone: +58-251-2591985 Fax: +58-251-2591886
Received: October 4, 2014
Peer-review started: October 5, 2014
First decision: November 14, 2014
Revised: February 7, 2015
Accepted: March 18, 2015
Article in press: March 20, 2015
Published online: May 20, 2015
Processing time: 229 Days and 11.5 Hours
Abstract

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/β-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors (mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput “omics” approaches will help in the search for Wnt pathway antagonist in the near future.

Keywords: Gastric cancer; Wnt; β-catenin; Oncogene; Tumor suppressor; Epigenetics; Helicobacter pylori; Adenomatous polyposis coli

Core tip: Available data indicate that Wnt signaling substantially impacts gastric tumorigenesis, prognosis, and resistance to therapy. Loss of Wnt signaling inhibitors (such as APC) by promoter hypermethylation, allelic loss or other mechanisms appear to be particularly important in activating Wnt/β-catenin signaling. Gastric cancer is an entity characterized by its heterogeneity in various aspects, and much remains to be learned about the molecular aspects that determine the process of cancer development in this organ. The role that plays the canonical Wnt pathway in gastric carcinogenesis is reviewed.