Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

Escaffit, Fabrice; Paré, Frédéric; Gauthier, Rémy; Rivard, Nathalie; Boudreau, François; Beaulieu, Jean‐François

doi:10.1016/j.bbrc.2006.01.128

Cited by 39 publications

(41 citation statements)

References 33 publications

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“…Therefore, this hypothesis was further investigated using the human normal intestinal epithelial crypt HIEC cells (Perreault and Beaulieu, 1996). Previous studies on HIEC cells showed that they expressed intestinal epithelial crypt cell markers such as epithelial keratins, junctional proteins, a trace of DPPIV, MIM-1/39, integrin a6b4, a8b1 and a9b1 (Perreault and Beaulieu, 1996;Desloges et al, 1998;Basora et al, 1999;Pageot et al, 2000;Benoit et al, 2009;Beaulieu and Ménard, 2012) but no Ecadherin, CDX2, HNF1a or SI (Escaffit et al, 2005a;Escaffit et al, 2005b;Escaffit et al, 2006;Benoit et al, 2010). Forced expression of CDX2 and HNF1a in HIEC resulted in the expression of polarization/junctional markers such as E-and Licadherin, a decrease in the expression of stem cell related markers such as DCAMKL1 and Mushashi-1 and the induction of SI and DPPIV expression (Benoit et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Polycomb repressive complex 2 impedes intestinal cell terminal differentiation

Benoit

Lepage

Khalfaoui

et al. 2012

Journal of Cell Science

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SummaryThe crypt-villus axis constitutes the functional unit of the small intestine, where mature absorptive cells are confined to the villi, and stem cells and transit amplifying and differentiating cells are restricted to the crypts. The polycomb group (PcG) proteins repress differentiation and promote self-renewal in embryonic stem cells. PcGs prevent transcriptional activity by catalysing epigenetic modifications, such as the covalent addition of methyl groups on histone tails, through the action of the polycomb repressive complex 2 (PRC2). Although a role for PcGs in the preservation of stemness characteristics is now well established, recent evidence suggests that they may also be involved in the regulation of differentiation. Using intestinal epithelial cell models that recapitulate the enterocytic differentiation programme, we generated a RNAi-mediated stable knockdown of SUZ12, which constitutes a cornerstone for PRC2 assembly and functionality, in order to analyse intestinal cell proliferation and differentiation. Expression of SUZ12 was also investigated in human intestinal tissues, revealing the presence of SUZ12 in most proliferative epithelial cells of the crypt and an increase in its expression in colorectal cancers. Moreover, PRC2 disruption led to a significant precocious expression of a number of terminal differentiation markers in intestinal cell models. Taken together, our data identified a mechanism whereby PcG proteins participate in the repression of the enterocytic differentiation program, and suggest that a similar mechanism exists in situ to slow down terminal differentiation in the transit amplifying cell population.

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Section: Discussionmentioning

confidence: 99%

Polycomb repressive complex 2 impedes intestinal cell terminal differentiation

Benoit

Lepage

Khalfaoui

et al. 2012

Journal of Cell Science

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“…Moreover, it was recently shown that CDX2 alters the proliferation of intestinal crypt cells and stimulates the expression of distinct intestinal differentiation markers 14,15 . We therefore examined CDX2 mRNA by Real-Time PCR in T84 cells co-cultured with normal, CD or UC LPL for 4 days (Fig 3).…”

Section: Lpl Induce An Increase In the Expression Of Cdx-2 In Colomentioning

confidence: 99%

“…In contrast to CDX1 which is mainly expressed in the crypt compartment (although not restricted to proliferative cells) 14 , the CDX2 homeoproteins are mainly expressed in differentiating enterocytes 15 , triggering growth retardation and cell differentiation by overexpression in several intestinal lines in vitro 16 . Furthermore, genes regulated by either CDX1 or CDX2 generally define a functional differentiated phenotype, such as sucraseisomaltase 16 , dipeptidyl peptidase IV 14 , or intestinal alkaline phosphatase (IAP) 15 .…”

Section: Introductionmentioning

confidence: 99%

Epithelial: Lamina Propria Lymphocyte Interactions Promote Epithelial Cell Differentiation

et al. 2008

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“…This transcriptional repression is mediated by CDX2-binding sites at nt À694 and nt À676 from initiation. Although CDX2 has been shown to regulate negatively gene expression (Guo et al, 2004;Escaffit et al, 2006), these are the first data to demonstrate that CDX2 can act as a transcriptional repressor. alter anchorage-dependent colony formation in either cell lines (data not shown).…”

Section: Cdx2 Represses Igfbp-3 Promoter Activitymentioning

confidence: 80%

CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3

et al. 2007

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CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. We have reported that CDX2 promotes tumorigenicity in a subset of human colorectal cancer cell lines. Here, we present evidence that CDX2 negatively regulates the welldocumented growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3). Specifically, CDX2 binds to the IGFBP-3 gene promoter and can repress IGFBP-3 transcription, protein expression and secretion. Furthermore, inhibition of IGFBP-3 partially rescues the decreased anchorage-independent growth phenotype observed in CDX2 knockout cells. These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3.

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Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

Cited by 39 publications

References 33 publications

Polycomb repressive complex 2 impedes intestinal cell terminal differentiation

Polycomb repressive complex 2 impedes intestinal cell terminal differentiation

Epithelial: Lamina Propria Lymphocyte Interactions Promote Epithelial Cell Differentiation

CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3

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