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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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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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Canonical Wnt Signaling Pathway02:54

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Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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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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Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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Catenins01:23

Catenins

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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.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
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Tumor Progression02:07

Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
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Related Experiment Video

Updated: Apr 17, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Moving upstream in the war on WNTs.

David M Virshup

    The Journal of Clinical Investigation
    |February 18, 2015
    PubMed
    Summary

    Cholangiocarcinoma, a rare biliary duct cancer, is often refractory to treatment. Targeting the WNT/β-catenin pathway, upregulated by macrophages in tumors, shows therapeutic potential by reducing cancer growth.

    Area of Science:

    • Oncology
    • Cancer Biology
    • Immunology

    Background:

    • Cholangiocarcinoma (CCA) is a rare biliary duct cancer with poor treatment outcomes.
    • The underlying molecular drivers of CCA remain incompletely understood.
    • Chronic liver fluke infection is an established risk factor for CCA.

    Purpose of the Study:

    • To investigate the role of WNT/β-catenin signaling in sporadic cholangiocarcinoma.
    • To identify the cellular source of WNT ligands in CCA.
    • To evaluate therapeutic strategies targeting WNT signaling in preclinical models.

    Main Methods:

    • Analysis of WNT/β-catenin pathway activation in human CCA samples.
    • Depletion and inhibition of macrophages in animal models of CCA.
    • Pharmacological inhibition of WNT secretion and β-catenin activity in vivo.

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    Main Results:

    • WNT/β-catenin signaling is upregulated in sporadic cholangiocarcinoma.
    • Macrophages were identified as a major source of WNT ligands within CCA tumors.
    • Macrophage depletion or inhibition significantly reduced tumor burden and proliferation in preclinical models.
    • Pharmacological targeting of WNT secretion or β-catenin activity demonstrated efficacy in animal models.

    Conclusions:

    • Macrophage-derived WNT signaling is a key driver of cholangiocarcinoma.
    • Targeting WNT signaling pathways presents a promising therapeutic strategy for cholangiocarcinoma.
    • Inhibition of WNT secretion or β-catenin activity may be effective in treating CCA.