Targeting FGFR4 abrogates HNF1A-driven metastasis in pancreatic ductal adenocarcinoma.

ABSTRACT:

Background

We previously identified an oncogenic role for the transcription factor HNF1A in pancreatic ductal adenocarcinoma (PDAC). However, the role of HNF1A in the metastatic progression of PDAC remains unknown and targeting modalities for HNF1A-dependent phenotypes have yet to be identified.

Methods

Transwell chambers were used to assess the effects of HNF1A and FGFR4 modulation on the migration and invasion of ATCC and patient-derived PDAC cells in vitro. An intrasplenic injection xenograft model was used to evaluate the impact of HNF1A knockdown and overexpression on metastatic tumor burden. Single-cell RNA sequencing (scRNA-seq), tissue microarray (TMA) data, and UMAP spatial profiling were used to identify FGFR4 as an HNF1A target gene upregulated in metastatic cells

SUBMITTER: Crawford KJ 

PROVIDER: S-EPMC12306140 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature