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  Epithelial calcineurin controls microbiota-dependent intestinal tumor development

Peuker, K., Muff, S., Wang, J., Künzel, S., Bosse, E., Zeissig, Y., et al. (2016). Epithelial calcineurin controls microbiota-dependent intestinal tumor development. Nature Medicine, 22(5), 506. doi:10.1038/nm.4072https://www.nature.com/articles/nm.4072supplementary-information.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-9023-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-9024-B
Genre: Journal Article

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https://www.nature.com/articles/nm.4072 (Publisher version)
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 Creators:
Peuker, Kenneth1, Author
Muff, Stefanie, Author
Wang, Jun2, Author              
Künzel, Sven1, Author              
Bosse, Esther, Author
Zeissig, Yvonne, Author
Luzzi, Giuseppina, Author
Basic, Marijana, Author
Strigli, Anne, Author
Ulbricht, Andrea, Author
Kaser, Arthur, Author
Arlt, Alexander, Author
Chavakis, Triantafyllos, Author
van den Brink, Gijs R., Author
Schafmayer, Clemens, Author
Egberts, Jan-Hendrik, Author
Becker, Thomas, Author
Bianchi, Marco E., Author
Bleich, André, Author
Röcken, Christoph, Author
Hampe, Jochen, AuthorSchreiber, Stefan, AuthorBaines, John F.2, Author              Blumberg, Richard S., AuthorZeissig, Sebastian, Author more..
Affiliations:
1Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445635              
2Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445638              

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 Abstract: Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We demonstrate that calcineurin and NFAT factors are constitutively expressed by primary IECs and selectively activated in intestinal tumors as a result of impaired stratification of the tumor-associated microbiota and toll-like receptor signaling. Epithelial calcineurin supports the survival and proliferation of cancer stem cells in an NFAT-dependent manner and promotes the development of intestinal tumors in mice. Moreover, somatic mutations that have been identified in human CRC are associated with constitutive activation of calcineurin, whereas nuclear translocation of NFAT is associated with increased death from CRC. These findings highlight an epithelial cell–intrinsic pathway that integrates signals derived from the commensal microbiota to promote intestinal tumor development.

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Language(s): eng - English
 Dates: 2015-12-102016-02-292016-04-042016
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
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Title: Nature Medicine
  Other : Nat. Med.
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Co.
Pages: 14 Volume / Issue: 22 (5) Sequence Number: - Start / End Page: 506 Identifier: ISSN: 1078-8956
CoNE: /journals/resource/954925606824