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A CRISPR knockout screen reveals new regulators of canonical Wnt signaling
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. A...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458386/ https://www.ncbi.nlm.nih.gov/pubmed/34552058 http://dx.doi.org/10.1038/s41389-021-00354-7 |
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author | Evron, Tamar Caspi, Michal Kazelnik, Michal Shor-Nareznoy, Yarden Armoza-Eilat, Shir Kariv, Revital Manber, Zohar Elkon, Ran Sklan, Ella H. Rosin-Arbesfeld, Rina |
author_facet | Evron, Tamar Caspi, Michal Kazelnik, Michal Shor-Nareznoy, Yarden Armoza-Eilat, Shir Kariv, Revital Manber, Zohar Elkon, Ran Sklan, Ella H. Rosin-Arbesfeld, Rina |
author_sort | Evron, Tamar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8458386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84583862021-10-07 A CRISPR knockout screen reveals new regulators of canonical Wnt signaling Evron, Tamar Caspi, Michal Kazelnik, Michal Shor-Nareznoy, Yarden Armoza-Eilat, Shir Kariv, Revital Manber, Zohar Elkon, Ran Sklan, Ella H. Rosin-Arbesfeld, Rina Oncogenesis Article 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. Nature Publishing Group UK 2021-09-22 /pmc/articles/PMC8458386/ /pubmed/34552058 http://dx.doi.org/10.1038/s41389-021-00354-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Evron, Tamar Caspi, Michal Kazelnik, Michal Shor-Nareznoy, Yarden Armoza-Eilat, Shir Kariv, Revital Manber, Zohar Elkon, Ran Sklan, Ella H. Rosin-Arbesfeld, Rina A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title | A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title_full | A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title_fullStr | A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title_full_unstemmed | A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title_short | A CRISPR knockout screen reveals new regulators of canonical Wnt signaling |
title_sort | crispr knockout screen reveals new regulators of canonical wnt signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458386/ https://www.ncbi.nlm.nih.gov/pubmed/34552058 http://dx.doi.org/10.1038/s41389-021-00354-7 |
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