PXD058833

PXD058833 is an original dataset announced via ProteomeXchange.

Title	Targeting the NPY/NPY1R Signaling Axis in Mutant p53-Dependent Pancreatic Cancer Impairs Metastasis
Description	Pancreatic Cancer (PC) is a highly metastatic malignancy. Over 80% of PC patients present with advanced-stage disease, preventing potentially curative surgery. The Neuropeptide Y (NPY)system, best known for its role in controling energy homeostasis, has also been show to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. Here, we show that expression of NPY and NPY1R are upregulated in mouse PC models and human PC patients. Moreover, using the genetically engineered, autochthonous KPR172HC mouse model of PC we demonstrate that pancreas-specific and whole-body knockout of Npy1r significantly decreases metastasis to the liver. We identify that treatment with the NPY1R antagonist BIBO330485 significantly reduces KPR172HC migratory capacity on cell-derived matrices. Importantly, pharmacological NPY1R inhibition in an intrasplenic model of PC metastasis recapitulated the results of our genetic studies, with BIBO3304 significantly decreasing metastasis in the liver. Together, our results reveal that NPY/NPY1R signaling is a novel anti-metastatic target in PC.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:20:51.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brooke Pereira
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-12 18:24:18	ID requested
⏵ 1	2025-05-07 06:20:52	announced

Chambers CR, Watakul S, Schofield P, Howell AE, Zhu J, Tran AMH, Kuepper N, Reed DA, Murphy KJ, Channon LM, Pereira BA, Tyma VM, Lee V, Trpceski M, Henry J, Melenec P, Abdulkhalek L, Nobis M, Metcalf XL, Ritchie S, Cadell A, Stoehr J, Magenau A, Chacon-Fajardo D, Chitty JL, O'Connell S, Zaratzian A, Tayao M, Da Silva A, Lyons RJ, Goldstein LD, Dale A, Rookyard A, Connolly A, Crossett B, Tran YTH, Kaltzis P, Vennin C, Dinevska M, Croucher DR, Samra J, Mittal A, Weatheritt RJ, Philp A, Del Monte-Nieto G, Zhang L, Enriquez RF, Cox TR, Shi YC, Pinese M, Waddell N, Sim HW, Chtanova T, Wang Y, Joshua AM, Chantrill L, Evans TRJ, Gill AJ, Morton JP, Pajic M, Christ D, Herzog H, Timpson P, Herrmann D, Targeting the NPY/NPY1R signaling axis in mutant p53-dependent pancreatic cancer impairs metastasis. Sci Adv, 11(11):eadq4416(2025) [pubmed]

10.1126/sciadv.adq4416;

submitter keyword: pancreatic cancer, neuropeptide Y

Paul Timpson
contact affiliation	1. Garvan Institute of Medical Research, Cancer Ecosystems Program, and The Kinghorn Cancer Centre, Darlinghurst, Sydney, New South Wales, Australia. 2. School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales (UNSW), Kensington, Sydney, New South Wales, Australia.
contact email	p.timpson@garvan.org.au
lab head
Brooke Pereira
contact affiliation	Garvan Institute of Medical Research
contact email	b.pereira@garvan.org.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD058833

PRIDE project URI

• PRIDE
  1. PXD058833
     1. Label: PRIDE project
     2. Name: Targeting the NPY/NPY1R Signaling Axis in Mutant p53-Dependent Pancreatic Cancer Impairs Metastasis