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Related Concept Videos

Notch Signaling Pathway03:14

Notch 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...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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...
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Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

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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...
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
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Related Experiment Video

Updated: Feb 25, 2026

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

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Notch Shapes the Innate Immunophenotype in Breast Cancer.

Qiang Shen1, Brenda Cohen1, Weiyue Zheng1

  • 1Campbell Family Institute for Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada.

Cancer Discovery
|August 10, 2017
PubMed
Summary

Notch activation in basal-like breast cancer (BLBC) drives inflammation and macrophage recruitment. Targeting this pathway offers new immunotherapeutic strategies for aggressive BLBC.

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Area of Science:

  • Oncology
  • Immunology
  • Cell Signaling

Background:

  • Notch signaling is implicated in basal-like breast cancer (BLBC).
  • The tumor microenvironment significantly influences cancer progression.
  • Tumor-associated macrophages (TAMs) play a critical role in cancer development.

Purpose of the Study:

  • To investigate the role of Notch activation in shaping the tumor microenvironment in BLBC.
  • To elucidate the mechanisms by which Notch signaling influences cytokine production and immune cell recruitment.
  • To identify potential therapeutic targets for BLBC.

Main Methods:

  • Utilized a mouse model of spontaneous mammary carcinoma with regulated Notch signaling.
  • Analyzed gene expression arrays in human BLBC samples.
  • Assessed the expression of inflammatory cytokines (IL1β, CCL2) and macrophage infiltration.

Main Results:

  • Notch activation in tumor cells upregulates IL1β and CCL2, promoting TAM recruitment.
  • Notch signaling mediates a paracrine loop involving TAMs and tumor cells via TGFβ.
  • A strong correlation exists between Notch activation, cytokine production, macrophage infiltration, and BLBC in human patients.

Conclusions:

  • Notch signaling acts as a central regulator in a self-amplifying loop of inflammation and macrophage infiltration in BLBC.
  • Targeting Notch activation presents a promising immunotherapeutic strategy for BLBC.
  • Development of IL1β and CCL2 antagonists could offer rapid clinical impact for BLBC treatment.