Abstract
Genetic evidence suggests a role for the Wnt/β-catenin pathway in gastric cancer. However, Wnt5a, regarded as a prototypical non-canonical Wnt ligand, has also been extensively associated with this disease. Therefore, the roles of the Wnt signaling pathway in gastric cancer initiation and progression, and particularly the precise mechanisms by which the non-canonical Wnt pathway might promote the development and progression of gastric cancer, are not entirely well understood. This article analyzes publicly available gene and protein expression data and reveals the existence of a WNT5A/FZD2/FZD7/ROR2 signature, which correlates with tumor-infiltrating and mesenchymal cell marker expression. High expression of FZD7 and ROR2 correlates with a shared gene and protein expression profile, which in turn correlates with poor prognosis. In summary, the findings presented in this article provide an updated view of the relative contributions of the Wnt/β-catenin and non-canonical Wnt pathways in gastric cancer.
Highlights
The Wnt signaling pathway plays roles during embryonic development and adult homeostasis, and perturbation of this pathway is linked to several diseases (Logan and Nusse, 2004)
frizzled class receptor 2 (FZD2), FZD5, and frizzled class receptor 7 (FZD7) was significantly overexpressed in Gastric cancer (GC) samples (Figure 1A)
WNT5A, WNT2, and WNT10A were the only ligands overexpressed in GC samples
Summary
The Wnt signaling pathway plays roles during embryonic development and adult homeostasis, and perturbation of this pathway is linked to several diseases (Logan and Nusse, 2004) This pathway is commonly divided into two main branches. There is a subset of Wnt pathways that are independent of β-catenin, referred to as “non-canonical” (or “Wnt/β-catenin independent”) pathways (Semenov et al, 2007), which activate intracellular effectors, modulating cell behavior (Schlessinger et al, 2009) Aberrations in both pathways have been linked to cancer initiation and progression (Anastas and Moon, 2012; Kikuchi et al, 2012)
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