Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme.
YAP signalling
cancer biology
colon cancer
mouse
organoids
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
11 05 2022
11 05 2022
Historique:
received:
20
12
2021
accepted:
20
04
2022
entrez:
11
5
2022
pubmed:
12
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, using mouse intestinal organoids, we uncover a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative YAP-associated transcriptional programmes in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identify the glycoprotein thrombospondin-1 (THBS1) as the essential factor that mediates non-cell-autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the THBS1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells in intestinal tumours.
Identifiants
pubmed: 35543624
doi: 10.7554/eLife.76541
pii: 76541
pmc: PMC9094746
doi:
pii:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Jacquemin et al.
Déclaration de conflit d'intérêts
GJ, AW, MH, WS, ZH, CM, MP, FQ, SR, FD, GA, DL, DV, JP, SF No competing interests declared
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