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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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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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Regulation of Angiogenesis and Blood Supply01:24

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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...
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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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Metastasis02:30

Metastasis

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Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
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Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

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Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
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Lung Tumor Cell Recruitment Assay
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Endothelial Notch1 Activity Facilitates Metastasis.

Elfriede Wieland1, Juan Rodriguez-Vita1, Sven S Liebler2

  • 1Vascular Signaling and Cancer (A270), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Cancer Cell
|February 28, 2017
PubMed
Summary

Activated Notch1 signaling in endothelial cells promotes cancer metastasis by creating a pro-inflammatory environment. Blocking Notch1 or VCAM1 therapies can prevent metastasis and reduce neutrophil infiltration.

Keywords:
Notch signalingangiogenesisendothelial cellextravasationintravasationmetastasismouse modelsneutrophilssenescencevascular biology

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A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells
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A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells
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Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Endothelial cells (ECs) play a crucial role in tumor progression through angiocrine factors.
  • The Notch signaling pathway is implicated in various cellular processes, including cancer.

Purpose of the Study:

  • To investigate the role of activated Notch1 receptors in endothelial cells in cancer metastasis.
  • To determine the impact of sustained Notch1 signaling on the tumor microenvironment and metastatic potential.

Main Methods:

  • Analysis of Notch1 receptor activation in human carcinomas and melanoma ECs.
  • In vivo studies using mouse models of melanoma and ovarian carcinoma.
  • Assessment of EC senescence, chemokine expression, VCAM1, neutrophil infiltration, and tumor cell adhesion.
  • Evaluation of therapeutic interventions using Notch1 or VCAM1-blocking antibodies and genetic ablation of EC Notch signaling.

Main Results:

  • Activated Notch1 receptors (N1ICD) are prevalent in tumor ECs and correlate with reduced progression-free survival in melanoma.
  • Sustained N1ICD activity induces EC senescence, chemokine expression, and VCAM1 upregulation.
  • This promotes neutrophil infiltration, tumor cell adhesion, intravasation, and metastasis.
  • Targeting Notch1 or VCAM1 pathways, or ablating EC Notch signaling, inhibits metastasis and neutrophil infiltration.

Conclusions:

  • Sustained vascular Notch signaling drives metastasis by promoting a senescent, pro-inflammatory endothelium.
  • Targeting the Notch1 pathway and its downstream effectors like VCAM1 represents a potential therapeutic strategy against cancer metastasis.