PDGFRβ Signaling Cooperates with β-Catenin to Modulate c-Abl and Biologic Behavior of Desmoid-Type Fibromatosis.

ABSTRACT:

Purpose

This study sought to identify β-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRβ), affect these targets to alter natural history or treatment response in patients.

Experimental design

In vitro experiments utilized primary desmoid cell lines to examine regulation of β-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies.

Results

CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a β-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoi

SUBMITTER: Hu J 

PROVIDER: S-EPMC10792363 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature