GSE239407 PDGFR β signaling cooperates with β-catenin to modulate c-Abl and biologic behavior of desmoid-type fibromatosis [RNA-seq II]

Contributors : Jia Hu ; Aimee M CragoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThe mechanisms underlying oncogenesis in desmoid-type fibromatosis are poorly understood. This project sought to understand how β-catenin may function to promote desmoid formation and how external signaling by PDGFRβ modulates this activity. To examine this question, RNA-seq was performed on CTNNB1 knock-downs. Gene set enrichment analysis suggested that the oncogene controlled HIF1 and angiogenesis pathways; expression of related genes accurately differentiated desmoids analyzed by U133A array from normal mesenchymal tissues. We identified c-ABL as a direct transcriptional target of β-catenin that promoted HIF1α expression in desmoid cells. We also noted that c-ABL activity was enhanced by PDGFRβ. PDGFRβ en hanced desmoid cell proliferation and c-ABL was necessary for desmoid proliferation. To identify potential markers of PDGFRβ/c-ABL activity in vivo, we assessed RNA-seq of desmoid cells treated with PDGF-BB. ERG1 transcription was highly upregulate and IHC of ERG1 was subsequently used to assess outcomes in desmoid patients with biopsies available for testing.

Source: GEO: Gene Expression Omnibus - November 1, 2023 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research