Upregulated GPRC5A disrupting the Hippo pathway promotes the proliferation and migration of pancreatic cancer cells via the cAMP-CREB axis

BACKGROUND: Pancreatic cancer has a high mortality rate worldwide, and is predicted to be third leading cause of death in the near future. However, the regulatory mechanisms that inhibit the progression of pancreatic cancer remain elusive. Currently, exploring the function and mechanisms of GPCRs (G-protein coupled receptors) is an important way to discover promising therapeutic targets for cancer. METHODS: GPRC5A expression was measured using real-time quantitative PCR, immunohistochemistry and western blot assays. Cell proliferation and migration were assessed using CCK-8, clone formation, wound-healing and transwell assays. A cytosolic/nuclear distribution experiment was used to detect the protein location transfer. A xenograft model of pancreatic cancer was established to explore the role of GPRC5A in vivo. RESULTS: GPRC5A expression was increased in pancreatic cancer, and disruption of GPRC5A expression inhibited tumor growth in vivo. Mechanistically, GPRC5A positively regulated the transcription of YAP1 through cAMP-CREB signaling. Moreover, we show that the proliferation and migration induced by GPRC5A in pancreatic cancer could be rescued by inhibiting YAP1 expression. CONCLUSIONS: GPRC5A interacts with the Hippo pathway to promote the progression of pancreatic cancer. These findings reveal an important crosstalk model and provide potential targets for pancreatic cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-023-00626-1.