The interplay between oxytocin receptor and YAP in regulating gastric cancer progression

Gastric cancer (GC) remains a lethal malignancy with limited therapeutic targets, while recent studies revealed YAP could be a promising target for GC treatment. In our study, we identify oxytocin receptor (OXTR) as an important regulator of Hippo/YAP axis. Through bioinformatics analysis, RNA sequencing analysis, functional research, and molecular mechanism research, we found that OXTR could facilitate Hippo/YAP axis, while YAP were shown to bind the OXTR promoter, enhancing its expression and establishing an interesting positive feedback loop. These findings propose the significance of OXTR in GC progression and its potential as a therapeutic target for YAP-driven cancer. Schematic representation of the interaction between OXTR and the Hippo-YAP pathway: The activation of OXTR leads to the formation of a complex with ARRB2, thereby outcompeting LATS1 and inhibiting its phosphorylation of YAP. This interaction increases YAP signaling activity, which in turn promotes the progression of gastric cancer. Furthermore, YAP can bind to the promoter region of OXTR, facilitating its expression and establishing a positive feedback loop. The use of the OXTR antagonist Atosiban to inhibit OXTR activity promotes the phosphorylation of LATS1 by ARRB2, which subsequently suppresses YAP phosphorylation. This results in the sequestration of YAP in the cytoplasm, thereby inhibiting the progression of gastric cancer.