American Association for Cancer Research
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Figure S7 from MYC Instructs and Maintains Pancreatic Adenocarcinoma Phenotype

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journal contribution
posted on 2023-04-03, 22:20 authored by Nicole M. Sodir, Roderik M. Kortlever, Valentin J.A. Barthet, Tania Campos, Luca Pellegrinet, Steven Kupczak, Panayiotis Anastasiou, Lamorna Brown Swigart, Laura Soucek, Mark J. Arends, Trevor D. Littlewood, Gerard I. Evan

Myc directly induces PD-L1/CD274 gene expression in KMpdx1 pancreatic epithelial cells


Cancer Research UK

European Research Council

Stand Up To Cancer



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 pancreatic intraepithelial neoplasm (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 drive 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. We show that Myc activation in indolent KrasG12D-induced PanIN epithelium acts as an immediate pleiotropic switch, triggering tissue-specific signals that instruct all the diverse signature stromal features of spontaneous human PDAC. Subsequent Myc deactivation or inhibition immediately triggers a program that coordinately disassembles PDAC back to PanIN.See related commentary by English and Sears, p. 495.

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