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Updated: Jul 9, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
Delta-like 4/Notch signaling and its therapeutic implications
1Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, CA 94080, USA. minhong@gene.com
Summary
Targeting Delta-like 4 (Dll4)-mediated Notch signaling, a key pathway in angiogenesis, shows promise for cancer therapy. Blocking Dll4/Notch signaling inhibits tumor growth by creating defective vasculature, offering a new strategy against treatment resistance.
Area of Science:
- Molecular biology
- Cancer research
- Vascular biology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and a target for cancer therapies.
- Vascular endothelial growth factor (VEGF) signaling is a validated target, with bevacizumab approved for certain cancers.
- Delta-like 4 (Dll4)-mediated Notch signaling is another critical pathway in vascular development and angiogenesis.
Purpose of the Study:
- To explore the role of Dll4-mediated Notch signaling in angiogenesis and its potential as a cancer therapy target.
- To understand the consequences of Dll4/Notch signaling attenuation on tumor vasculature and growth.
Main Methods:
- Review of recent studies on Dll4 function in angiogenesis.
- Analysis of preclinical data on the effects of Dll4/Notch signaling blockade.
Main Results:
- Dll4 acts downstream of VEGF, providing negative feedback on VEGF signaling.
- Attenuation of Dll4/Notch signaling leads to chaotic vascular networks with excessive sprouting.
- Blocking Dll4/Notch signaling paradoxically increases tumor vessel density but inhibits tumor growth due to defective vasculature.
Conclusions:
- Dll4/Notch signaling blockade is a promising strategy for antiangiogenesis cancer therapy.
- This approach may be particularly effective in overcoming resistance to existing therapies.
Related Concept Videos
03:14Notch 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 until 1985...
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 until 1985...
03:14Notch 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 until 1985...
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 until 1985...
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...
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
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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...