EGFR-activated myofibroblasts promote metastasis of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective treatment strategies. We previously identified transforming growth factor beta (TGF-β) as a main driver of myofibroblastic CAFs (myCAFs). Here, we show that epidermal growth factor receptor/Erb-B2 receptor (EGFR/ERBB2) signaling is induced by TGF-β in myCAFs through an autocrine process mediated by amphiregulin. Inhibition of this EGFR/ERBB2-signaling network in PDAC organoid-derived cultures and mouse models differentially impacts distinct CAF subtypes, providing…

• UD
  U.S. Department of Defense
• PC
  Pancreatic Cancer UK
• PC
  Pancreatic Cancer Research Fund
• UR
  UK Research and Innovation
• CR
  Cancer Research UK

  Award: A27463
• UO
  University of Cambridge
• GC
  Gates Cambridge Trust
• MR
  Medical Research Council
• CR
  Cancer Research UK Cambridge Institute, University of Cambridge