HDAC4/MybL1/YAP novel signaling axis is required for pancreatic cancer metastasis to the liver.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of human malignancy, and there is an urgency to develop more effective therapy. We previously showed that Metavert, a dual inhibitor of glycogen synthase kinase 3-beta (GSK-3β) and histone deacetylases (HDACs) prevents pancreatic ductal adenocarcinoma (PDAC) metastasis. In this study, we investigated the mechanisms that mediate metastasis and the roles of GSK-3β, HDACs, and Yes-associated protein (YAP) in this process. We found that HDAC4 and YAP are highly expressed in PDAC from patients with rapid disease progression and metastasis compared to those with prolonged recurrence-free survival. Pan-HDAC inhibition decreases metastasis in the splenic PDAC metastatic mouse model. Inhibition of HDAC4 reduces migration of cance

SUBMITTER: Edderkaoui M 

PROVIDER: S-EPMC12631223 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature