Related Experiment Video

Updated: Mar 18, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

Dominique Bozec1,2, Alina C Iuga3, Giulia Roda4,5

  • 1Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Oncotarget
|June 27, 2016
PubMed

Insights

Receptor interacting protein kinase 3 (RIPK3) suppresses colorectal cancer (CRC) by controlling inflammation and cell proliferation. Loss of RIPK3 promotes tumor growth, highlighting its role as a colon tumor suppressor.

Area of Science:

  • Cell Biology
  • Immunology
  • Oncology

Background:

  • Necroptosis, a programmed cell death, is regulated by receptor interacting protein kinase 3 (RIPK3).
  • In vitro studies suggest RIPK3-deficient cancer cells are invasive, but its in vivo role in cancer remains unclear.

Purpose of the Study:

  • To investigate the physiological role of RIPK3 in colorectal cancer (CRC) development.
  • To determine if RIPK3 functions as a tumor suppressor in the intestine.

Main Methods:

  • Utilized RIPK3-deficient mice to study colitis-associated CRC.
  • Analyzed inflammatory mediators, tumor-promoting factors, and key signaling pathways (NF-κB, STAT3, AKT, Wnt-β-catenin).
  • Examined RIPK3 expression in human inflammatory bowel disease and CRC patient tumors.

Main Results:

  • RIPK3-deficient mice showed increased susceptibility to colitis-associated CRC with elevated pro-inflammatory and tumor-promoting factors.
  • Tumorigenesis in RIPK3-deficient mice was driven by uncontrolled NF-κB, STAT3, AKT, and Wnt-β-catenin signaling, promoting aberrant intestinal epithelial cell proliferation.
  • RIPK3 expression was reduced in human inflammatory bowel disease and CRC tumors, correlating with cancer progression.

Conclusions:

  • RIPK3 plays a critical role in suppressing colorectal cancer.
  • RIPK3 exhibits anti-inflammatory and anti-tumoral functions in the intestine.
  • RIPK3 is identified as a novel colon tumor suppressor, crucial for preventing CRC development.
Keywords:
IBD-related CRCRIPK3colorectal cancernecroptosis

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