| Literature DB >> 35121975 |
Karolina Slowicka1,2,3, Ioanna Petta1,3,4, Gillian Blancke1,3,4, Esther Hoste1,2, Emilie Dumas1,3,4, Mozes Sze1,2, Hanna Vikkula1,2, Enrico Radaelli5,6, Jody J Haigh7,8, Sven Jonckheere2,9, Joachim Taminau2,9, Niels Vandamme1,2,9, Andy Wullaert1,2,3,4, Eugene Tulchinsky10,11, David Nittner12,13, Pieter Van Vlierberghe9,14, Gert De Hertogh15, Pamela Baldin16, Emre Etlioglu13, Pratyaksha Wirapati17, Louis Boon18, Bart N Lambrecht1,4, Chris Callewaert19, Sabine Tejpar13, Steven Goossens2,9,14,20, Geert Berx21,22, Lars Vereecke23,24,25,26, Geert van Loo27,28,29,30.
Abstract
Colorectal cancer (CRC) is highly prevalent in Western society, and increasing evidence indicates strong contributions of environmental factors and the intestinal microbiota to CRC initiation, progression and even metastasis. We have identified a synergistic inflammatory tumor-promoting mechanism through which the resident intestinal microbiota boosts invasive CRC development in an epithelial-to-mesenchymal transition-prone tissue environment. Intestinal epithelial cell (IEC)-specific transgenic expression of the epithelial-to-mesenchymal transition regulator Zeb2 in mice (Zeb2IEC-Tg/+) leads to increased intestinal permeability, myeloid cell-driven inflammation and spontaneous invasive CRC development. Zeb2IEC-Tg/+ mice develop a dysplastic colonic epithelium, which progresses to severely inflamed neoplastic lesions while the small intestinal epithelium remains normal. Zeb2IEC-Tg/+ mice are characterized by intestinal dysbiosis, and microbiota depletion with broad-spectrum antibiotics or germ-free rederivation completely prevents cancer development. Zeb2IEC-Tg/+ mice represent the first mouse model of spontaneous microbiota-dependent invasive CRC and will help us to better understand host-microbiome interactions driving CRC development in humans.Entities:
Mesh：
Year: 2020 PMID： 35121975 DOI： 10.1038/s43018-020-0070-2
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347