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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.
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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.
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
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In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model
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Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1.

Hiroki Kobayashi1, Yosuke Ochiai1,2, Junya Arai1,3,4

  • 1Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.

Cancer Research
|December 31, 2025
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Summary
This summary is machine-generated.

Nerves influence cancer. The study found netrin-1 promotes pancreatic ductal adenocarcinoma (PDAC) progression by enhancing cancer stemness and metastasis, suggesting netrin-1 as a therapeutic target.

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Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • Nerves play a role in tumorigenesis and cancer progression.
  • The specific functions of axon guidance molecules in tumor development and metastasis require further investigation.

Purpose of the Study:

  • To investigate the role of axon guidance molecules, specifically netrin-1, in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis, innervation, and metastasis.
  • To explore the therapeutic potential of targeting the netrin-1 pathway in PDAC.

Main Methods:

  • Screening of axon guidance molecules in murine KrasG12D-mutant pancreatic organoids.
  • In vivo and ex vivo studies using mouse models (Pdx1-Cre;LSL-KrasG12D/+ and Pdx1-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+) and celiac ganglia cultures.
  • Analysis of netrin-1 and its receptor NEO1 expression, signaling pathways (MAPK, FAK), epithelial-mesenchymal transition (EMT), and cancer stemness markers (ZEB1, SOX9).

Main Results:

  • Netrin-1 was upregulated in PDAC and promoted sympathetic neuron axonogenesis via NEO1.
  • Netrin-1/NEO1 signaling enhanced PDAC cell growth, EMT, and stemness by activating FAK, leading to increased tumor progression and reduced survival in mice.
  • Inhibition of netrin-1 or NEO1 reduced tumor progression and metastasis in preclinical models.

Conclusions:

  • The netrin-1/NEO1 axis is a critical regulator of PDAC progression, influencing cancer cell stemness and EMT, and promoting tumor growth via nerve interactions.
  • Targeting the netrin-1 pathway presents a promising therapeutic strategy for PDAC.