Related Experiment Video

Updated: Feb 28, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.3K

The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma

Myron S Ignatius1, Madeline N Hayes2, Riadh Lobbardi2

  • 1Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Center of Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Greehey Children's Cancer Research Institute and Department of Molecular Medicine, UT Health Sciences Center, San Antonio, TX 78229, USA.

Cell Reports
|June 15, 2017
PubMed

Insights

Intracellular NOTCH1 (ICN1) drives pediatric embryonal rhabdomyosarcoma (ERMS) growth by increasing tumor-propagating cells (TPCs). This NOTCH1/SNAI1/MEF2C pathway disrupts normal muscle differentiation, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Developmental Biology
  • Cancer Stem Cell Biology

Background:

  • Tumor-propagating cells (TPCs) are crucial for sustained tumor growth and share self-renewal properties with normal stem cells.
  • The mechanisms governing TPC self-renewal remain largely unknown, particularly in embryonal rhabdomyosarcoma (ERMS), a prevalent pediatric muscle cancer.

Purpose of the Study:

  • To investigate the role of intracellular NOTCH1 (ICN1) in regulating TPC self-renewal and differentiation in ERMS.
  • To elucidate the molecular mechanisms by which ICN1 influences TPC expansion and muscle differentiation.

Main Methods:

  • Utilized a zebrafish transgenic model of ERMS to study TPC dynamics.
  • Analyzed the expression and function of NOTCH1, SNAIL1, and MEF2C in both zebrafish and human ERMS cells.
  • Investigated the impact of ICN1 on cell differentiation and self-renewal capacity.

Main Results:

  • Identified that ICN1 significantly increased TPCs by 23-fold in a zebrafish ERMS model.
  • Demonstrated that ICN1 promotes TPC self-renewal by enabling dedifferentiation of ERMS cells, overriding normal muscle differentiation hierarchies.
  • Confirmed conserved roles for ICN1 in human ERMS self-renewal and growth, mechanistically linked to SNAIL1 upregulation and MEF2C suppression.

Conclusions:

  • The NOTCH1/SNAI1/MEF2C signaling axis is a key determinant of TPC self-renewal and differentiation in ERMS.
  • Targeting this pathway presents a promising future therapeutic strategy for ERMS treatment.
Keywords:
MEF2CNOTCH1SNAI1de-differentiationmusclerhabdomyosarcomaself-renewaltumor propagating cellszebrafish

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

9.9K

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...
6.7K
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...
2.5K
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...
4.9K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.3K
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...
5.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K