Ap4 is rate limiting for intestinal tumor formation by controlling the homeostasis of intestinal stem cells

Stephanie Jaeckel, Markus Kaller, Rene Jackstadt, Ursula Götz, Susanna Müller, Sophie Boos, David Horst, Peter Jung and Heiko Hermeking ()
Additional contact information
Stephanie Jaeckel: Ludwig-Maximilians-Universität München
Markus Kaller: Ludwig-Maximilians-Universität München
Rene Jackstadt: Ludwig-Maximilians-Universität München
Ursula Götz: Ludwig-Maximilians-Universität München
Susanna Müller: Ludwig-Maximilians-Universität München
Sophie Boos: Ludwig-Maximilians-Universität München
David Horst: Ludwig-Maximilians-Universität München
Peter Jung: Ludwig-Maximilians-Universität München
Heiko Hermeking: Ludwig-Maximilians-Universität München

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract The gene encoding the transcription factor TFAP4/AP4 represents a direct target of the c-MYC oncoprotein. Here, we deleted Ap4 in ApcMin mice, a preclinical model of inherited colorectal cancer. Ap4 deficiency extends their average survival by 110 days and decreases the formation of intestinal adenomas and tumor-derived organoids. The effects of Ap4 deletion are presumably due to the reduced number of functional intestinal stem cells (ISCs) amenable to adenoma-initiating mutational events. Deletion of Ap4 also decreases the number of colonic stem cells and increases the number of Paneth cells. Expression profiling revealed that ISC signatures, as well as the Wnt/β-catenin and Notch signaling pathways are downregulated in Ap4-deficient adenomas and intestinal organoids. AP4-associated signatures are conserved between murine adenomas and human colorectal cancer samples. Our results establish Ap4 as rate-limiting mediator of adenoma initiation, as well as regulator of intestinal and colonic stem cell and Paneth cell homeostasis.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06001-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06001-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06001-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().