Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer.
Biological sciences
Cancer
Cell biology
Functional aspects of cell biology
Oncology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
17 Dec 2021
17 Dec 2021
Historique:
received:
27
01
2021
revised:
18
08
2021
accepted:
11
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
9
12
2021
Statut:
epublish
Résumé
Retinoic acid (RA) signaling is an important and conserved pathway that regulates cellular proliferation and differentiation. Furthermore, perturbed RA signaling is implicated in cancer initiation and progression. However, the mechanisms by which RA signaling contributes to homeostasis, malignant transformation, and disease progression in the intestine remain incompletely understood. Here, we report, in agreement with previous findings, that activation of the Retinoic Acid Receptor and the Retinoid X Receptor results in enhanced transcription of enterocyte-specific genes in mouse small intestinal organoids. Conversely, inhibition of this pathway results in reduced expression of genes associated with the absorptive lineage. Strikingly, this latter effect is conserved in a human organoid model for colorectal cancer (CRC) progression. We further show that RXR motif accessibility depends on progression state of CRC organoids. Finally, we show that reduced RXR target gene expression correlates with worse CRC prognosis, implying RA signaling as a putative therapeutic target in CRC.
Identifiants
pubmed: 34877501
doi: 10.1016/j.isci.2021.103444
pii: S2589-0042(21)01415-2
pmc: PMC8633980
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103444Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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