A CRISPR knockout screen reveals new regulators of canonical Wnt signaling.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
22 Sep 2021
22 Sep 2021
Historique:
received:
09
08
2021
accepted:
01
09
2021
revised:
18
08
2021
entrez:
23
9
2021
pubmed:
24
9
2021
medline:
24
9
2021
Statut:
epublish
Résumé
The Wnt signaling pathways play fundamental roles during both development and adult homeostasis. Aberrant activation of the canonical Wnt signal transduction pathway is involved in many diseases including cancer, and is especially implicated in the development and progression of colorectal cancer. Although extensively studied, new genes, mechanisms and regulatory modulators involved in Wnt signaling activation or silencing are still being discovered. Here we applied a genome-scale CRISPR-Cas9 knockout (KO) screen based on Wnt signaling induced cell survival to reveal new inhibitors of the oncogenic, canonical Wnt pathway. We have identified several potential Wnt signaling inhibitors and have characterized the effects of the initiation factor DExH-box protein 29 (DHX29) on the Wnt cascade. We show that KO of DHX29 activates the Wnt pathway leading to upregulation of the Wnt target gene cyclin-D1, while overexpression of DHX29 inhibits the pathway. Together, our data indicate that DHX29 may function as a new canonical Wnt signaling tumor suppressor and demonstrates that this screening approach can be used as a strategy for rapid identification of novel Wnt signaling modulators.
Identifiants
pubmed: 34552058
doi: 10.1038/s41389-021-00354-7
pii: 10.1038/s41389-021-00354-7
pmc: PMC8458386
doi:
Types de publication
Journal Article
Langues
eng
Pagination
63Informations de copyright
© 2021. The Author(s).
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