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The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms
Developmental genes contribute to cancer, as reported for the homeobox gene Cdx2 playing a tumor suppressor role in the gut. In this study, we show that human colon cancers exhibiting the highest reduction in CDX2 expression belong to the serrated subtype with the worst evolution. In mice, mosaic kn...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839756/ https://www.ncbi.nlm.nih.gov/pubmed/29439001 http://dx.doi.org/10.1084/jem.20170934 |
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author | Balbinot, Camille Armant, Olivier Elarouci, Nabila Marisa, Laetitia Martin, Elisabeth De Clara, Etienne Onea, Alina Deschamps, Jacqueline Beck, Felix Freund, Jean-Noël Duluc, Isabelle |
author_facet | Balbinot, Camille Armant, Olivier Elarouci, Nabila Marisa, Laetitia Martin, Elisabeth De Clara, Etienne Onea, Alina Deschamps, Jacqueline Beck, Felix Freund, Jean-Noël Duluc, Isabelle |
author_sort | Balbinot, Camille |
collection | PubMed |
description | Developmental genes contribute to cancer, as reported for the homeobox gene Cdx2 playing a tumor suppressor role in the gut. In this study, we show that human colon cancers exhibiting the highest reduction in CDX2 expression belong to the serrated subtype with the worst evolution. In mice, mosaic knockout of Cdx2 in the adult intestinal epithelium induces the formation of imperfect gastric-type metaplastic lesions. The metaplastic knockout cells do not spontaneously become tumorigenic. However, they induce profound modifications of the microenvironment that facilitate the tumorigenic evolution of adjacent Cdx2-intact tumor-prone cells at the surface of the lesions through NF-κB activation, induction of inducible nitric oxide synthase, and stochastic loss of function of Apc. This study presents a novel paradigm in that metaplastic cells, generally considered as precancerous, can induce tumorigenesis from neighboring nonmetaplastic cells without themselves becoming cancerous. It unveils the novel property of non–cell-autonomous tumor suppressor gene for the Cdx2 gene in the gut. |
format | Online Article Text |
id | pubmed-5839756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58397562018-09-05 The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms Balbinot, Camille Armant, Olivier Elarouci, Nabila Marisa, Laetitia Martin, Elisabeth De Clara, Etienne Onea, Alina Deschamps, Jacqueline Beck, Felix Freund, Jean-Noël Duluc, Isabelle J Exp Med Research Articles Developmental genes contribute to cancer, as reported for the homeobox gene Cdx2 playing a tumor suppressor role in the gut. In this study, we show that human colon cancers exhibiting the highest reduction in CDX2 expression belong to the serrated subtype with the worst evolution. In mice, mosaic knockout of Cdx2 in the adult intestinal epithelium induces the formation of imperfect gastric-type metaplastic lesions. The metaplastic knockout cells do not spontaneously become tumorigenic. However, they induce profound modifications of the microenvironment that facilitate the tumorigenic evolution of adjacent Cdx2-intact tumor-prone cells at the surface of the lesions through NF-κB activation, induction of inducible nitric oxide synthase, and stochastic loss of function of Apc. This study presents a novel paradigm in that metaplastic cells, generally considered as precancerous, can induce tumorigenesis from neighboring nonmetaplastic cells without themselves becoming cancerous. It unveils the novel property of non–cell-autonomous tumor suppressor gene for the Cdx2 gene in the gut. Rockefeller University Press 2018-03-05 /pmc/articles/PMC5839756/ /pubmed/29439001 http://dx.doi.org/10.1084/jem.20170934 Text en © 2018 Balbinot et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Balbinot, Camille Armant, Olivier Elarouci, Nabila Marisa, Laetitia Martin, Elisabeth De Clara, Etienne Onea, Alina Deschamps, Jacqueline Beck, Felix Freund, Jean-Noël Duluc, Isabelle The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title | The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title_full | The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title_fullStr | The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title_full_unstemmed | The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title_short | The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
title_sort | cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839756/ https://www.ncbi.nlm.nih.gov/pubmed/29439001 http://dx.doi.org/10.1084/jem.20170934 |
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