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

Related Experiment Video

Updated: Feb 5, 2026

Intestinal Stem Cell Isolation and Culture in a Porcine Model of Segmental Small Intestinal Ischemia
08:55

Intestinal Stem Cell Isolation and Culture in a Porcine Model of Segmental Small Intestinal Ischemia

Published on: May 18, 2018

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Stephanie Jaeckel1, Markus Kaller1, Rene Jackstadt1

  • 1Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Thalkirchner Strasse 36, D-80337, Munich, Germany.

Nature Communications
|September 5, 2018
PubMed

Insights

Deleting the TFAP4/AP4 gene in mice significantly extended survival and reduced intestinal tumors by impacting intestinal stem cells (ISCs). This finding highlights AP4

Area of Science:

  • Molecular Biology
  • Oncology
  • Gastroenterology

Background:

  • The transcription factor TFAP4/AP4 is a direct target of the c-MYC oncoprotein.
  • Colorectal cancer (CRC) is a significant health concern, with inherited forms often modeled in mice.

Purpose of the Study:

  • To investigate the role of TFAP4/AP4 in inherited colorectal cancer using a preclinical mouse model.
  • To determine the impact of Ap4 deficiency on intestinal stem cell (ISC) function and tumor initiation.

Main Methods:

  • Deletion of the Ap4 gene in ApcMin mice, a model for inherited colorectal cancer.
  • Assessment of survival rates, intestinal adenoma formation, and tumor-derived organoids.
  • Analysis of colonic stem cell populations, Paneth cell numbers, and gene expression profiling.

Main Results:

  • Ap4 deficiency extended average survival by 110 days and reduced intestinal adenoma formation.
  • Ap4 deletion decreased the number of functional intestinal stem cells (ISCs) and colonic stem cells.
  • Downregulation of ISC signatures and Wnt/β-catenin and Notch signaling pathways observed in Ap4-deficient models.

Conclusions:

  • TFAP4/AP4 acts as a rate-limiting mediator in adenoma initiation.
  • Ap4 regulates intestinal and colonic stem cell homeostasis and Paneth cell differentiation.
  • AP4-associated molecular signatures in mouse models are conserved in human colorectal cancer.

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