Nuclear VAV1 increases GLI1-dependent transcription in pancreatic cancer cells.

ABSTRACT: The oncogenic role of VAV1, a GTPase guanine nucleotide exchange factor (GEF) with cytoplasmic and nuclear localizations, has been previously reported in multiple malignancies. Most of the mechanisms underlying this pro-tumoral activity have been linked to the cytoplasmic expression of this GEF. To date, the contribution of nuclear VAV1 to cancer development remains poorly understood. Here, using models of pancreatic ductal adenocarcinomas (PDAC), the most common subtype of pancreatic cancer, we provide evidence of a novel mechanism driving oncogenic gene expression in PDAC cells that is regulated by nuclear VAV1. We show that VAV1 wild-type, unlike its mutant lacking the nuclear localization signal (NLS), localizes to the nucleus of PDAC cells where it increases GLI transcriptional activi

SUBMITTER: Tader BR 

PROVIDER: S-EPMC12765065 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature