Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells.
Nat Commun
; 9(1): 1132, 2018 03 19.
Article
em En
| MEDLINE
| ID: mdl-29556067
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Transformação Celular Neoplásica
/
Via de Sinalização Wnt
/
Carcinogênese
/
Mucosa Intestinal
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido