Related Experiment Video

Updated: Feb 4, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.7K

The Proto-oncogene c-Kit Inhibits Tumor Growth by Behaving as a Dependence Receptor

Hong Wang1, Amina Boussouar1, Laetitia Mazelin1

  • 1Apoptosis, Cancer and Development Laboratory - Equipe labellisée "La Ligue," LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon1, Centre Léon Bérard, 69008 Lyon, France.

Molecular Cell
|October 9, 2018
PubMed

Insights

The proto-oncogene c-Kit, normally promoting cancer, also triggers cell death in cancer cells. This tumor-suppressive function is revealed when c-Kit kinase activity is blocked and involves its cleavage.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • c-Kit is a proto-oncogene implicated in cancer via mutations or upregulation, leading to uncontrolled cell proliferation.
  • Some observations suggest c-Kit may have roles beyond tumor promotion, prompting further investigation into its dual function.

Purpose of the Study:

  • To investigate the dual role of c-Kit in cancer, specifically its potential tumor-suppressive functions.
  • To elucidate the mechanisms underlying c-Kit's pro-death activity and its regulation.

Main Methods:

  • Experiments involving various cancer cell lines to assess c-Kit's effect on cell death.
  • Analysis of c-Kit cleavage by caspase-like proteases at D816.
  • In vivo studies using c-Kit kinase-dead mutants to evaluate tumor growth inhibition.

Main Results:

  • c-Kit actively triggers cancer cell death unless bound by its ligand, stem cell factor (SCF).
  • This pro-death activity is amplified when c-Kit kinase activity is inhibited and results from intracellular cleavage at D816.
  • Overexpression of a kinase-dead c-Kit mutant suppressed tumor growth in vivo, dependent on D816 cleavage.

Conclusions:

  • c-Kit exhibits a dual role in cancer, acting as a proto-oncogene through its kinase activity and as a tumor suppressor via its dependence receptor activity.
  • The tumor-suppressive function of c-Kit is linked to its ligand-independent pro-death signaling, mediated by caspase-like cleavage at D816.
Keywords:
SCFapoptosisc-Kitcancercaspasedependence receptorsreceptor tyrosine kinase

More Related Videos

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.8K
Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells10:21

Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells

Published on: January 5, 2018

13.7K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
11.5K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.1K
Frequency-dependent Selection01:21

Frequency-dependent Selection

When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
24.1K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.7K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.4K
Drug Dependence01:17

Drug Dependence

Medications are typically administered to achieve therapeutic effects. Some drugs can modify an individual's mood and perception, frequently resulting in various enjoyable experiences. However, this can result in drug dependency, a condition marked by continuous drug use despite potential negative consequences. Drug dependency primarily falls into two categories: psychological and physical dependence. Psychological dependence occurs when the pleasurable feelings induced by the drug...
1.7K