Metaplastic Cdx2-depleted cells can be very disruptive neighbors.
The Journal of experimental medicine
Rockefeller University Press
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Lourenço, F. C., & Winton, D. (2018). Metaplastic Cdx2-depleted cells can be very disruptive neighbors.. The Journal of experimental medicine, 215 (3), 725-727. https://doi.org/10.1084/jem.20180215
In this issue of JEM, Balbinot et al. describe an original mechanism where Cdx2 inactivation regulates intestinal metaplastic to neoplastic transition in a paracrine fashion. Surprisingly the target cells are neighbouring “normal” Cdx2 positive cells. The homeodomain or homeobox protein family are transcription factors that present a conserved DNA-binding domain that play a vital role in spatial patterning during embryogenesis. Their function has been first described in Drosophila (Scott and O'Farrell, 1986) and is conserved throughout evolution to vertebrates (De Robertis et al., 1989; Wright et al., 1989). Cdx2 is a homeodomain protein whose expression in the murine late embryo and adult is confined to the epithelium of the intestine. It has a pivotal role in the establishment of endodermal anterior-posterior (AP) asymmetry and more specifically intestinal identity. Cdx2 null mice are not viable and die before gastrulation however heterozygote Cdx2 are viable with some mice presenting developmental abnormalities such as stunted growth or rib malformation. Strikingly these mice have multiple adenomatous polyps, mostly in the proximal colon, displaying several areas of squamous metaplasia with loss of the remaining wild-type Cdx2 allele (Chawengsaksophak et al., 1997). Mosaic conditional Cdx2 knock-out in the adult intestine resulted in impairment of stem cell differentiation with gradual loss of villous morphology and formation of cystic vesicles. When aged these mice present caecal polyps with Cdx-2 negative regions displaying gastric features (Stringer et al., 2012).
Animals, Mice, Transgenic, Mice, Homeodomain Proteins, Genes, Homeobox, Carcinogenesis, CDX2 Transcription Factor
Cancer Research UK (CB4230)
Cancer Research UK (C14303_do not transfer)
External DOI: https://doi.org/10.1084/jem.20180215
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275385
Attribution-NonCommercial-ShareAlike 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-sa/4.0/
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