The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non-cell-autonomous mechanisms.
Fiche publication
Date publication
mars 2018
Journal
The Journal of experimental medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DULUC Isabelle, Dr FREUND Jean-Noël
Tous les auteurs :
Balbinot C, Armant O, Elarouci N, Marisa L, Martin E, De Clara E, Onea A, Deschamps J, Beck F, Freund JN, Duluc I
Lien Pubmed
Résumé
Developmental genes contribute to cancer, as reported for the homeobox gene playing a tumor suppressor role in the gut. In this study, we show that human colon cancers exhibiting the highest reduction in expression belong to the serrated subtype with the worst evolution. In mice, mosaic knockout of 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 -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 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 gene in the gut.
Mots clés
Animals, CDX2 Transcription Factor, genetics, Carcinogenesis, genetics, Cecum, pathology, Colonic Neoplasms, genetics, Gene Expression Regulation, Neoplastic, Heterozygote, Humans, Intestinal Neoplasms, genetics, Intestines, pathology, Metaplasia, Mice, NF-kappa B, metabolism, Neoplastic Stem Cells, metabolism, Nitric Oxide Synthase Type II, metabolism, Stromal Cells, metabolism, Tumor Microenvironment
Référence
J. Exp. Med.. 2018 Mar 5;215(3):911-926