Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer

Summary: 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, mal...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Roelof A. Wester, Lisa van Voorthuijsen, Hannah K. Neikes, Jelmer J. Dijkstra, Lieke A. Lamers, Siebren Frölich, Maarten van der Sande, Colin Logie, Rik G.H. Lindeboom, Michiel Vermeulen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Cancer Cell biology Functional aspects of cell biology Oncology Science Q
Acceso en línea:	https://doaj.org/article/ee53bbefaa5245eea4b658c2b77ce466
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ee53bbefaa5245eea4b658c2b77ce466
record_format	dspace
spelling	oai:doaj.org-article:ee53bbefaa5245eea4b658c2b77ce4662021-11-28T04:36:30ZRetinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer2589-004210.1016/j.isci.2021.103444https://doaj.org/article/ee53bbefaa5245eea4b658c2b77ce4662021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014152https://doaj.org/toc/2589-0042Summary: 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.Roelof A. WesterLisa van VoorthuijsenHannah K. NeikesJelmer J. DijkstraLieke A. LamersSiebren FrölichMaarten van der SandeColin LogieRik G.H. LindeboomMichiel VermeulenElsevierarticleBiological sciencesCancerCell biologyFunctional aspects of cell biologyOncologyScienceQENiScience, Vol 24, Iss 12, Pp 103444- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Cancer Cell biology Functional aspects of cell biology Oncology Science Q
spellingShingle	Biological sciences Cancer Cell biology Functional aspects of cell biology Oncology Science Q Roelof A. Wester Lisa van Voorthuijsen Hannah K. Neikes Jelmer J. Dijkstra Lieke A. Lamers Siebren Frölich Maarten van der Sande Colin Logie Rik G.H. Lindeboom Michiel Vermeulen Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
description	Summary: 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.
format	article
author	Roelof A. Wester Lisa van Voorthuijsen Hannah K. Neikes Jelmer J. Dijkstra Lieke A. Lamers Siebren Frölich Maarten van der Sande Colin Logie Rik G.H. Lindeboom Michiel Vermeulen
author_facet	Roelof A. Wester Lisa van Voorthuijsen Hannah K. Neikes Jelmer J. Dijkstra Lieke A. Lamers Siebren Frölich Maarten van der Sande Colin Logie Rik G.H. Lindeboom Michiel Vermeulen
author_sort	Roelof A. Wester
title	Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
title_short	Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
title_full	Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
title_fullStr	Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
title_full_unstemmed	Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
title_sort	retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ee53bbefaa5245eea4b658c2b77ce466
work_keys_str_mv	AT roelofawester retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT lisavanvoorthuijsen retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT hannahkneikes retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT jelmerjdijkstra retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT liekealamers retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT siebrenfrolich retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT maartenvandersande retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT colinlogie retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT rikghlindeboom retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer AT michielvermeulen retinoicacidsignalingdrivesdifferentiationtowardtheabsorptivelineageincolorectalcancer
_version_	1718408294309036032

Retinoic acid signaling drives differentiation toward the absorptive lineage in colorectal cancer

Ejemplares similares