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Zeb2 drives invasive and microbiota-dependent colon carcinoma

Karolina Slowicka (UGent) , Ioanna Petta (UGent) , Gillian Blancke (UGent) , Esther Hoste (UGent) , Emilie Dumas (UGent) , Mozes Sze (UGent) , Hanna-Kaisa Vikkula (UGent) , Enrico Radaelli, Jody J. Haigh, Sven Jonckheere (UGent) , et al.
(2020) NATURE CANCER. 1(6). p.620-634
Author
Organization
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.
Keywords
POOR-PROGNOSIS SUBTYPES, COLORECTAL-CANCER, INTESTINAL HOMEOSTASIS, KAPPA-B, INFLAMMATION, EXPRESSION, CELL, EMT, IMMUNITY, GENES

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MLA
Slowicka, Karolina, et al. “Zeb2 Drives Invasive and Microbiota-Dependent Colon Carcinoma.” NATURE CANCER, vol. 1, no. 6, 2020, pp. 620–34, doi:10.1038/s43018-020-0070-2.
APA
Slowicka, K., Petta, I., Blancke, G., Hoste, E., Dumas, E., Sze, M., … van Loo, G. (2020). Zeb2 drives invasive and microbiota-dependent colon carcinoma. NATURE CANCER, 1(6), 620–634. https://doi.org/10.1038/s43018-020-0070-2
Chicago author-date
Slowicka, Karolina, Ioanna Petta, Gillian Blancke, Esther Hoste, Emilie Dumas, Mozes Sze, Hanna-Kaisa Vikkula, et al. 2020. “Zeb2 Drives Invasive and Microbiota-Dependent Colon Carcinoma.” NATURE CANCER 1 (6): 620–34. https://doi.org/10.1038/s43018-020-0070-2.
Chicago author-date (all authors)
Slowicka, Karolina, Ioanna Petta, Gillian Blancke, Esther Hoste, Emilie Dumas, Mozes Sze, Hanna-Kaisa Vikkula, Enrico Radaelli, Jody J. Haigh, Sven Jonckheere, Joachim Taminau, Niels Vandamme, Andy Wullaert, Eugene Tulchinsky, David Nittner, Pieter Van Vlierberghe, Gert De Hertogh, Pamela Baldin, Emre Etlioglu, Pratyaksha Wirapati, Louis Boon, Bart Lambrecht, Chris Callewaert, Sabine Tejpar, Steven Goossens, Geert Berx, Lars Vereecke, and Geert van Loo. 2020. “Zeb2 Drives Invasive and Microbiota-Dependent Colon Carcinoma.” NATURE CANCER 1 (6): 620–634. doi:10.1038/s43018-020-0070-2.
Vancouver
1.
Slowicka K, Petta I, Blancke G, Hoste E, Dumas E, Sze M, et al. Zeb2 drives invasive and microbiota-dependent colon carcinoma. NATURE CANCER. 2020;1(6):620–34.
IEEE
[1]
K. Slowicka et al., “Zeb2 drives invasive and microbiota-dependent colon carcinoma,” NATURE CANCER, vol. 1, no. 6, pp. 620–634, 2020.
@article{8680036,
  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.}},
  author       = {{Slowicka, Karolina and Petta, Ioanna and Blancke, Gillian and Hoste, Esther and Dumas, Emilie and Sze, Mozes and Vikkula, Hanna-Kaisa and Radaelli, Enrico and Haigh, Jody J. and Jonckheere, Sven and Taminau, Joachim and Vandamme, Niels and Wullaert, Andy and Tulchinsky, Eugene and Nittner, David and Van Vlierberghe, Pieter and De Hertogh, Gert and Baldin, Pamela and Etlioglu, Emre and Wirapati, Pratyaksha and Boon, Louis and Lambrecht, Bart and Callewaert, Chris and Tejpar, Sabine and Goossens, Steven and Berx, Geert and Vereecke, Lars and van Loo, Geert}},
  issn         = {{2662-1347}},
  journal      = {{NATURE CANCER}},
  keywords     = {{POOR-PROGNOSIS SUBTYPES,COLORECTAL-CANCER,INTESTINAL HOMEOSTASIS,KAPPA-B,INFLAMMATION,EXPRESSION,CELL,EMT,IMMUNITY,GENES}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{620--634}},
  title        = {{Zeb2 drives invasive and microbiota-dependent colon carcinoma}},
  url          = {{http://dx.doi.org/10.1038/s43018-020-0070-2}},
  volume       = {{1}},
  year         = {{2020}},
}

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