Related Experiment Video

Updated: Aug 13, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

8.8K

Notch Signaling Suppresses Melanoma Tumor Development in BRAF/Pten Mice

Dareen Mikheil1, Kirthana Prabhakar1, Tun Lee Ng2

  • 1Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.

Cancers
|January 21, 2023
PubMed

Insights

Notch signaling has dual roles in melanoma development. Loss of Notch1 or Notch2 accelerates tumor growth in a Pten-null background, suggesting a tumor suppressor role in melanoma progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Notch signaling exhibits contradictory roles in melanoma, acting as both oncogenic and tumor-suppressive.
  • Clinical trials show Notch inhibitors are ineffective for melanoma treatment.
  • Notch signaling influences melanoma transdifferentiation, a key prognostic factor.

Purpose of the Study:

  • To investigate the role of Notch signaling in melanoma tumor development and growth.
  • To elucidate the specific functions of Notch1 and Notch2 in BRAFV600E-driven melanomagenesis.
  • To explore the correlation between Notch protein levels and clinical parameters in human melanoma.

Main Methods:

  • Utilized a genetic mouse model of melanoma by crossing specific BRAF and Pten mutant mice with Notch1 or Notch2 floxed alleles.
  • Induced tumors via tamoxifen application in genetically modified mice.
  • Performed quantitative immunochemical analysis on a human cutaneous melanoma tissue microarray (>100 primary tumors).

Main Results:

  • Loss of Notch1 or Notch2 did not substitute for Pten's tumor suppressor function in BRAFV600E-induced melanomagenesis.
  • In a Pten-null background, loss of Notch1 or Notch2 accelerated BRAFV600E-induced tumor development.
  • A weak to moderate correlation was observed between NOTCH protein levels and clinical/pathological parameters in human melanoma.

Conclusions:

  • Notch1 and Notch2 act as tumor suppressors in the context of BRAFV600E/Pten-null driven melanomagenesis.
  • Notch signaling is implicated in melanoma development.
  • Identifying downstream targets of Notch signaling may offer new avenues for melanoma prevention strategies.
Keywords:
Notch signalingmelanomamelanoma TMAmelanoma mouse modelmelanoma tumor development

More Related Videos

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

3.0K
Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model10:23

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model

Published on: November 13, 2012

13.8K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K
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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K