The Hippo and Wnt signalling pathways: crosstalk during neoplastic progression in gastrointestinal tissue

The Hippo and Wnt signalling pathways play crucial roles in maintaining tissue homeostasis and organ size by orchestrating cell proliferation, differentiation and apoptosis. These pathways have been frequently found to be dysregulated in human cancers. While the canonical signal transduction of Hippo and Wnt has been well studied, emerging evidence shows that these two signalling pathways contribute to and exhibit overlapping functions in gastrointestinal (GI) tumorigenesis. In fact, the core effectors YAP/TAZ in Hippo signalling pathway cooperate with β‐catenin in Wnt signalling pathway to promote GI neoplasia. Here, we provide a brief review to summarize the molecular mechanisms underlying the crosstalk between these two pathways and elucidate their involvement in GI tumorigenesis, particularly focusing on the intestine, stomach and liver. The crosstalk between Hippo and Wnt signalling: (1) cytoplasmic YAP/TAZ is involved in the β‐catenin destruction complex; (2) the E3 ubiquitin ligase β‐TrCP is responsible for YAP/TAZ and β‐catenin degradation; (3) nuclear YAP can form a complex with β‐catenin, resulting in the cooperation of YAP/TAZ with β‐catenin to induce cell proliferation and drive tumourigenesis.