Abstract 1224 PRSS8 functions as an endogenous TβRIII sheddase via a novel cholesterol-PRSS8-TGF-β axis

TGF-β signaling is frequently dysregulated in a diverse set of cancer types and can contribute to multiple cancer-associated phenotypes including avoidance of apoptosis, immune evasion, epithelial to mesenchymal transition, migration, and metastasis. The pathway is canonically activated by TGF-β ligand binding to and heterotetramerization of two molecules of TβRI and two molecules of TβRII. This leads to phosphorylation of the SMAD2/3 transcription factors that translocate to the nucleus alongside SMAD4 to transcriptionally regulate its target genes.