Evidence map›Paper›PMID 40702342›Full record

ArticleEMBO reports2025

Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes.

Declan Whyte, Sophie L Fisher, Christopher G J McKenzie, David Sumpton, Sandeep Dhayade, Emmanuel Dornier, Madeleine Moore, David Novo, Jasmine Peters, Robert Wiesheu and 31 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

41 authors.

Declan WhyteCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0009-0705-2296
Sophie L FisherCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0004-9298-2386
Christopher G J McKenzieCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0006-6909-7375
David SumptonCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-9004-4079
Sandeep DhayadeCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-1681-8216
Emmanuel DornierCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-3482-8637
Madeleine MooreCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0003-5246-3955
David NovoCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0001-5344-0083
Jasmine PetersCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0008-5938-5749
Robert WiesheuCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-2079-4413
Michalis D GounisCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0001-7142-4677
Dale M WattCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-0443-176X
John B G MackeyCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-2189-5590
Amanda J McFarlaneCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
Frédéric FercoqCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-4825-024X
Carolina Dehesa CaballeroSchool of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK.ORCID 0000-0001-7193-8141
Keara L RedmondQueen's University Belfast, University Rd, Belfast, BT7 1NN, UK.
Louise E MitchellCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0004-3173-5074
Eve AndersonCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0002-8727-4639
Gemma ThomsonCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0003-0336-0167
Ann HedleyCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0000-2752-0936
William ClarkCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0004-8982-8564
Shannen LeroiSchool of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK.ORCID 0009-0002-0770-5815
Lindsey N DzierozynskiBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.ORCID 0009-0000-6641-0211
Juan J Apiz SaabBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.ORCID 0000-0002-4799-9291
Caroline A LewisWhitehead Institute for Biomedical Research, Cambridge, MA, USA.ORCID 0000-0003-1787-5084
Alexander MuirBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.ORCID 0000-0003-3811-3054
Christopher J HalbrookDepartment of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.ORCID 0000-0002-3376-3114
Douglas StrathdeeCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0003-2959-4327
Rene JackstadtCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0009-0005-6246-2133
Colin NixonCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-8085-2160
Philip DunneCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0001-9160-283X
Leo M CarlinCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0001-7172-5234
Iain R MacphersonSchool of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1QH, UK.ORCID 0000-0003-4295-8885
Edward W RobertsCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-8229-1715
Seth B CoffeltCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0003-2257-2862
Karen BlythCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0002-9304-439X
Owen J SansomCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.ORCID 0000-0001-9540-3010
Jim C NormanCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. j.norman@crukscotlandinstitute.ac.uk.ORCID 0000-0002-0098-3014
Johan Vande VoordeCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. johan.vandevoorde@glasgow.ac.uk.ORCID 0000-0002-7686-0926
Cassie J ClarkeCancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. c.clarke@crukscotlandinstitute.ac.uk.ORCID 0000-0003-2232-1609

Funding

Breast Cancer Now (BCN) 2019NovPR1268Cancer Research UK (CRUK) A18277Cancer Research UK (CRUK) A273110Cancer Research UK (CRUK) A28291Cancer Research UK (CRUK) A29799Cancer Research UK (CRUK) A31287Cancer Research UK (CRUK) PRCBTP-May24/100005Cancer Research UK (CRUK) RCCCDF-Nov23/100001Pancreatic Cancer UK (PCUK) 2021RIF_22_VoordeUKRI | Medical Research Council (MRC) MC_PC_21042UKRI | Medical Research Council (MRC) MR/P01058X/1Wellcome TrustWellcome Trust 318046
6 · The paper itself

Abstract

Understanding mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis. Here we identify uracil as a metastasis-associated metabolite in genetically engineered mouse models of cancer and in patients with metastatic breast cancer. Uracil is generated by the enzyme uridine phosphorylase-1 (UPP1), and we find that neutrophils are a significant source of UPP1 in metastatic cancer. Mammary tumours increase expression of adhesion molecules on the neutrophil surface, in a UPP1-dependent manner, leading to decreased neutrophil motility in the pre-metastatic lung. UPP1-expressing neutrophils suppress T-cell proliferation, and the UPP1 product uracil increases fibronectin deposition in the extracellular microenvironment. Knockout or inhibition of UPP1 in mice with mammary tumours increases T-cell numbers and reduces fibronectin content in the lung, and decreases the proportion of mice that develop lung metastasis. These data indicate that UPP1 influences neutrophil behaviour and extracellular matrix deposition in the lung, and suggest that circulating uracil could be a marker of metastasis, and that pharmacological inhibition of UPP1 could be a strategy to reduce recurrence.

Indexed as

Breast NeoplasmsExtracellular MatrixUridine PhosphorylaseAnimalsCell Line, TumorCell ProliferationFemaleFibronectinsHumansLung NeoplasmsMiceMice, KnockoutNeoplasm MetastasisNeutrophilsT-LymphocytesTumor MicroenvironmentFibronectinsUracilUridine PhosphorylaseFibronectinMetastasisNeutrophilsT CellsUridine Phosphorylase

Identifiers

PMID40702342
PMCPMC12420820

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.