Ral GTPase promotes metastasis of pancreatic ductal adenocarcinoma via elevation of TGF-β1 production.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), caused by activating mutations in K-Ras, is an aggressive malignancy due to its early invasion and metastasis. Ral GTPases are activated downstream of Ras and play a crucial role in the development and progression of PDAC. However, the underlying mechanisms remain unclear. In this study, we investigated the mechanism of Ral-induced invasion and metastasis of PDAC cells using RalGAPβ-deficient PDAC cells with highly activated Ral GTPases. Array analysis and ELISA revealed increased expression and secretion of TGF-β1 in RalGAPβ-deficient PDAC cells compared to control cells. Blockade of TGF-β1 signaling suppressed RalGAPβ deficiency-enhanced migration and invasion in vitro and metastasis in vivo to levels similar to controls. Phosphorylation of c-Jun

SUBMITTER: Cao M 

PROVIDER: S-EPMC10220265 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature