MYC instructs and maintains pancreatic adenocarcinoma phenotype

Nicole M. Sodir, Roderik M. Kortlever, Valentin J.A. Barthet, Tania Campos, Luca Pellegrinet, Steven Kupczak, Panayiotis Anastasiou, Lamorna Brown Swigart, Laura Soucek, Mark Arends, Trevor J. Littlewood, Gerard I Evan

Research output: Contribution to journalArticlepeer-review

Abstract

The signature features of pancreatic ductal adenocarcinoma (PDAC) are its fibroinflammatory stroma, poor immune activity and dismal prognosis. We show that acute activation of Myc in indolent PanIN epithelial cells in vivo is, alone, sufficient to trigger immediate release of instructive signals that together coordinate changes in multiple stromal and immune cell types and trigger transition to pancreatic adenocarcinomas that share all the characteristic stromal features of their spontaneous human counterpart. We also demonstrate that this Myc-driven PDAC switch is completely and immediately reversible: Myc deactivation/inhibition triggers meticulous disassembly of advanced PDAC tumor and stroma and concomitant death of tumor cells. Hence, both the formation and deconstruction of the complex PDAC phenotype are continuously dependent on a single, reversible Myc switch.
Original languageEnglish
Pages (from-to)588-607
Number of pages30
JournalCancer Discovery
Volume10
Issue number4
Early online date15 Jan 2020
DOIs
Publication statusPublished - 12 Mar 2020

Keywords

  • Myc
  • Ras
  • pancreatic cancer
  • microenvironment
  • immune evasion

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