Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function.
Nature
; 529(7584): 97-100, 2016 Jan 07.
Article
de En
| MEDLINE
| ID: mdl-26700806
ABSTRACT
Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules souches tumorales
/
Tumeurs colorectales
/
Différenciation cellulaire
/
Thrombospondines
/
Receptor-Like Protein Tyrosine Phosphatases, Class 2
/
Thérapie moléculaire ciblée
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Nature
Année:
2016
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique