Targeting the NPY/NPY1R signaling axis in mutant p53–dependent pancreatic cancer impairs metastasis

Authors: Cecilia R. Chambers, Supitchaya Watakul, Peter Schofield, Anna E. Howell, Jessie Zhu, Alice M. H. Tran, Nadia Kuepper, Daniel A. Reed, Kendelle J. Murphy, Lily M. Channon, Brooke A. Pereira, Victoria M. Tyma, Victoria Lee, Michael Trpceski, Jake Henry, Pauline Melenec, Lea Abdulkhalek, Max Nobis, Xanthe L. Metcalf, Shona Ritchie, Antonia Cadell, Janett Stoehr, Astrid Magenau, Diego Chacon-Fajardo, Jessica L. Chitty, Savannah O’Connell, Anaiis Zaratzian, Michael Tayao, Andrew Da Silva, Ruth J. Lyons, Leonard D. Goldstein, Ashleigh Dale, Alexander Rookyard, Angela Connolly, Ben Crossett, Yen T. H. Tran, Peter Kaltzis, Claire Vennin, Marija Dinevska, , , David R. Croucher, Jaswinder Samra, Anubhav Mittal, Robert J. Weatheritt, Andrew Philp, Gonzalo Del Monte-Nieto, Lei Zhang, Ronaldo F. Enriquez, Thomas R. Cox, Yan-Chuan C. Shi, Mark Pinese, Nicola Waddell, Hao-Wen Sim, Tatyana Chtanova, Yingxiao Wang, Anthony M. Joshua, Lorraine Chantrill, Thomas R. Jeffry Evans, Anthony J. Gill, Jennifer P. Morton, Marina Pajic, Daniel Christ, Herbert Herzog, Paul Timpson, David Herrmann

Published: 2025-03-12

DOI: 10.1126/sciadv.adq4416

Source: Full article


Abstract

Pancreatic cancer (PC) is a highly metastatic malignancy. More than 80% of patients with PC present with advanced-stage disease, preventing potentially curative surgery. The neuropeptide Y (NPY) system, best known for its role in controlling energy homeostasis, has also been shown to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. We show that expression of NPY and