The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non-cell-autonomous mechanisms
© 2018 Balbinot et al..
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.
| Errataetall: |
CommentIn: J Exp Med. 2018 Mar 5;215(3):725-727. - PMID 29440363 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:215 |
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| Enthalten in: |
The Journal of experimental medicine - 215(2018), 3 vom: 05. März, Seite 911-926 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Balbinot, Camille [VerfasserIn] |
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| Links: |
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| Themen: |
CDX2 Transcription Factor |
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| Anmerkungen: |
Date Completed 01.04.2019 Date Revised 01.04.2019 published: Print-Electronic CommentIn: J Exp Med. 2018 Mar 5;215(3):725-727. - PMID 29440363 Citation Status MEDLINE |
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| doi: |
10.1084/jem.20170934 |
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| PPN (Katalog-ID): |
NLM280978650 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Elarouci, Nabila |e verfasserin |4 aut | |
| 700 | 1 | |a Marisa, Laetitia |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Elisabeth |e verfasserin |4 aut | |
| 700 | 1 | |a De Clara, Etienne |e verfasserin |4 aut | |
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| 700 | 1 | |a Deschamps, Jacqueline |e verfasserin |4 aut | |
| 700 | 1 | |a Beck, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Freund, Jean-Noël |e verfasserin |4 aut | |
| 700 | 1 | |a Duluc, Isabelle |e verfasserin |4 aut | |
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