Related Experiment Video

Updated: Nov 5, 2025

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
08:37

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

Published on: April 21, 2015

17.0K

RIPK3 Suppresses the Progression of Spontaneous Intestinal Tumorigenesis

Qun Zhao1, Jian Guo1, Xinran Cheng1

  • 1Laboratory of Inflammation and Molecular Pharmacology, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan, China.

Frontiers in Oncology
|May 17, 2021
PubMed

Insights

Receptor-interacting protein 3 (RIPK3) acts as a tumor suppressor in intestinal cancer. Targeting IL-6/STAT3 signaling may benefit patients with reduced RIPK3, improving prognosis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Death Pathways

Background:

  • Receptor-interacting protein 3 (RIPK3) is a serine/threonine protein kinase involved in necroptosis.
  • Downregulated RIPK3 expression correlates with poor prognosis in various cancers, including colorectal cancer (CRC).

Purpose of the Study:

  • To investigate the role of RIPK3 in spontaneous intestinal tumorigenesis.
  • To explore the association between RIPK3 expression and clinical features in CRC patients.
  • To identify potential therapeutic targets for intestinal tumors with reduced RIPK3.

Main Methods:

  • Utilized RIPK3-deficient (Ripk3) mice in a spontaneous intestinal tumorigenesis model (Apc).
  • Analyzed tumor formation, histological grade, and lymphatic metastasis.
  • Investigated the IL-6/STAT3 signaling pathway in Apc tumors.
  • Assessed the effect of blocking IL-6 signaling on tumor development.

Main Results:

  • RIPK3 deficiency accelerated tumor formation in Apc mice.
  • Reduced RIPK3 expression in CRC patients correlated with higher histological grade, lymphatic metastasis, and poorer prognosis.
  • Apc tumors exhibited hyperactivated IL-6/STAT3 signaling, promoting proliferation and inhibiting apoptosis.
  • Blocking IL-6 signaling suppressed tumor formation and STAT3 activation in Apc mice.

Conclusions:

  • RIPK3 functions as a tumor suppressor in spontaneous intestinal tumorigenesis.
  • Targeting the IL-6/STAT3 signaling axis represents a potential therapeutic strategy for intestinal tumors with low RIPK3 expression.
Keywords:
APC mutant mouse modelIL-6 receptor antibodyRIPK3STAT3 (signal transducer and activator of transcription 3)intestinal tumorigenesis

More Related Videos

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy05:21

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy

Published on: October 6, 2014

9.9K
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

9.7K

Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.4K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.9K