Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells

D. J. Huels, L. Bruens, M. C. Hodder, P. Cammareri, A. D. Campbell, R. A. Ridgway, D. M. Gay, M. Solar-Abboud, W. J. Faller, C. Nixon, L. B. Zeiger, M. E. McLaughlin, E. Morrissey, D. J. Winton, H. J. Snippert, J. van Rheenen and O. J. Sansom ()
Additional contact information
D. J. Huels: CRUK Beatson Institute
L. Bruens: Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht
M. C. Hodder: CRUK Beatson Institute
P. Cammareri: CRUK Beatson Institute
A. D. Campbell: CRUK Beatson Institute
R. A. Ridgway: CRUK Beatson Institute
D. M. Gay: CRUK Beatson Institute
M. Solar-Abboud: CRUK Beatson Institute
W. J. Faller: CRUK Beatson Institute
C. Nixon: CRUK Beatson Institute
L. B. Zeiger: CRUK Beatson Institute
M. E. McLaughlin: Novartis Institutes for Biomedical Research
E. Morrissey: John Radcliffe Hospital
D. J. Winton: CRUK Cambridge Institute
H. J. Snippert: University Medical Center Utrecht
J. van Rheenen: Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht
O. J. Sansom: CRUK Beatson Institute

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03426-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03426-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03426-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().