Related Experiment Video
Updated: Feb 17, 2026
10:37
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
36.6K
Numb prevents a complete epithelial-mesenchymal transition by modulating Notch signalling
Federico Bocci1,2, Mohit K Jolly1, Satyendra C Tripathi3
1Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
Journal of the Royal Society, Interface
|December 1, 2017
Summary
Numb protein inhibits full epithelial-mesenchymal transition (EMT), stabilizing a hybrid E/M phenotype crucial for metastasis. This suggests Numb
Area of Science:
- Cell Biology
- Cancer Research
- Computational Biology
Background:
- Epithelial-mesenchymal transition (EMT) is vital for development, healing, and cancer metastasis.
- Hybrid epithelial/mesenchymal (E/M) phenotype cells drive metastasis via collective migration.
- Notch signaling promotes EMT, but cluster formation mechanisms are unclear.
Purpose of the Study:
- Investigate Numb's role in EMT and cluster formation.
- Understand Numb's function as an inhibitor of Notch signaling.
- Examine Numb's impact on hybrid E/M phenotype stability.
Main Methods:
- Integrated computational modeling and experimental validation.
- Mathematical modeling of Numb's effect on EMT.
- Numb knockdown experiments in H1975 cells.
- Analysis of multi-cell dynamics and tumor-initiation potential.
Main Results:
- Numb stabilizes the hybrid E/M phenotype, inhibiting full EMT.
- Numb knockdown in hybrid E/M cells induced a full EMT.
- Mathematical models predicted Numb alters cell balance in clusters.
- Numb correlates with poorer survival in lung and ovarian cancers.
Conclusions:
- Numb acts as a phenotypic stability factor by modulating Notch-driven EMT.
- Numb influences cluster composition and potentially tumor-initiation ability.
- Numb's association with poor survival highlights its role in cancer aggressiveness.
Related Concept Videos
03:14Notch Signaling Pathway
6.7K
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...
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
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.5K
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...
2.5K
01:19Cadherins in Tissue Organization
4.3K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
4.3K
01:26Stem Cell Niche
6.4K
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
6.4K
02:33Hedgehog Signaling Pathway
10.2K
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...
10.2K
01:24Regulation of Angiogenesis and Blood Supply
3.6K
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...
3.6K