Astudillo Besnier, Pablo

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.

To date, most data regarding the crosstalk between the Wnt signaling pathway and the YAP/TAZ transcriptional coactivators focuses on the Wnt/β-catenin branch of the pathway. In contrast, the relationship between the non-canonical Wnt pathway and YAP/TAZ remains significantly less explored. Wnt5a is usually regarded as a prototypical non-canonical Wnt ligand, and its expression has been related to cancer progression. On the other hand, YAP/TAZ transcriptional coactivators act in concert with TEAD transcription factors to control gene expression. Although one article has shown previously that WNT5A is a YAP/TEAD target gene, there is a need for further evidence supporting this regulatory relationship, because a possible YAP/Wnt5a regulatory circuit might have profound implications for cancer biology. This article analyzes publicly available ChIP-Seq, gene expression, and protein expression data to explore this relationship, and shows that WNT5A might be a YAP/TEAD target gene in several contexts. Moreover, Wnt5a and YAP expression are significantly correlated in specific cancer types, suggesting that the crosstalk between YAP/TAZ and the Wnt pathway is more intricate than previously thought.