Published online May 20, 2015. doi: 10.5493/wjem.v5.i2.84
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
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.
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.