Related Experiment Video
Updated: Jul 8, 2026
03:23
Fluorescent Laparoscopic Central Hepatectomy for Liver Cancer Using Indocyanine Green Negative Staining
Published on: March 17, 2023
Netrin-1 controls colorectal tumorigenesis by regulating apoptosis
Laetitia Mazelin1, Agnès Bernet, Christelle Bonod-Bidaud
1Apoptosis/Differentiation Laboratory-Equipe labellisée La Ligue-Molecular and Cellular Genetic Center, CNRS UMR 5534, University of Lyon, 69622 Villeurbanne, France.
Nature
|September 3, 2004
Summary
Netrin-1 binding to its receptor DCC (deleted in colorectal cancer) prevents cell death, promoting intestinal tumor development. This suggests DCC and its receptors act as conditional tumor suppressors, impacting cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Deleted in colorectal cancer (DCC) protein expression is reduced in many cancers, suggesting a tumor suppressor role.
- Doubts exist regarding DCC's tumor suppressor function due to rare mutations and lack of predisposition in mutant mice.
- DCC acts as a dependence receptor, inducing apoptosis unless bound by its ligand, netrin-1.
Purpose of the Study:
- To investigate the role of netrin-1 in intestinal tumor development.
- To determine if netrin-1 signaling influences cell survival and cancer progression.
Main Methods:
- Enforced expression of netrin-1 in the mouse gastrointestinal tract.
- Analysis of tumor formation in wild-type and adenomatous polyposis coli (APC) mutant mice with enforced netrin-1 expression.
Main Results:
- Enforced netrin-1 expression led to spontaneous hyperplastic and neoplastic lesions in the mouse gut.
- In APC mutant mice, enforced netrin-1 expression resulted in aggressive adenocarcinomas.
- Netrin-1 appears to promote intestinal tumor development by regulating cell survival.
Conclusions:
- Netrin-1 signaling can drive intestinal tumor development.
- Netrin-1 receptors function as conditional tumor suppressors, regulating cell survival in the context of cancer.
Related Concept Videos
01:12Loss 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...
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:20The 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,...
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,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss 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...
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...
01:12Role 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...
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...