Related Experiment Video

Updated: Mar 24, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
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Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

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NLRX1 Acts as an Epithelial-Intrinsic Tumor Suppressor through the Modulation of TNF-Mediated Proliferation

Ivan Tattoli1, Samuel A Killackey2, Elisabeth G Foerster3

  • 1Department of Laboratory Medicine and Pathobiology, University of Toronto, M5S 1A8 Toronto, Canada; Department of Immunology, University of Toronto, M5S 1A8 Toronto, Canada.

Cell Reports
|March 15, 2016
PubMed

Insights

The mitochondrial protein NLRX1 suppresses colon cancer by regulating epithelial cell growth after injury. Loss of NLRX1 in intestinal cells leads to increased proliferation and promotes colitis-associated carcinogenesis.

Area of Science:

  • Cell Biology
  • Immunology
  • Gastroenterology

Background:

  • The role of NLRX1 in colorectal tumorigenesis is not fully understood.
  • NLRX1 is a mitochondrial Nod-like receptor protein involved in cellular processes.

Purpose of the Study:

  • To investigate the function of NLRX1 in intestinal epithelial cells (IECs) regarding colitis-associated carcinogenesis.
  • To elucidate the mechanisms by which NLRX1 impacts epithelial proliferation and tumorigenesis.

Main Methods:

  • Utilized mice with an IEC-specific deletion of Nlrx1.
  • Analyzed gene expression (Tnf, Egf, Tgfb1) and epithelial proliferation following dextran sodium sulfate (DSS) induced injury.
  • Studied primary intestinal organoids lacking Nlrx1 stimulated with TNF.
  • Assessed activation of Akt and NF-κB pathways.

Main Results:

  • NLRX1 deletion in IECs conferred protection against colitis-associated carcinogenesis.
  • Nlrx1 mutant mice showed increased Tnf, Egf, Tgfb1 expression and enhanced epithelial regeneration.
  • NLRX1-deficient organoids exhibited exacerbated proliferation and stem cell marker expression upon TNF stimulation.
  • Hyper-proliferation correlated with increased Akt and NF-κB pathway activation.

Conclusions:

  • NLRX1 acts as a suppressor of colonic tumorigenesis.
  • NLRX1 regulates intestinal epithelial proliferation during the regeneration phase after mucosal injury.
  • These findings highlight NLRX1's critical role in maintaining colon homeostasis and preventing cancer development.

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