PDGFRß signaling cooperates with ß-catenin to modulate c-Abl and biologic behavior of desmoid-type fibromatosis [RNA-seq I]
The mechanisms underlying oncogenesis in desmoid-type fibromatosis are poorly understood.  This project sought to understand how ß-catenin may function to promote desmoid formation and how external signaling by PDGFRß 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 ß-catenin that promoted HIF1a expression in desmoid cells.  We also noted that c-ABL activity was enhanced by PDGFRß.  PDGFRß enhanced desmoid cell proliferation and c-ABL was necessary for desmoid proliferation.  To identify potential markers of PDGFRß/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. Overall design: 1. Primary desmoid cell line DES9525 were treated with shRNA directed against CTNNB1, selected with antibiotic and RNA-seq analyzed on both CTNNB1 knock-downs and scramble controls 2. Primary desmoid cell line DES9525 was treated with PDGF-BB (20ng/ml) for 24 hours and RNA-seq performed on both treated and untreated cells