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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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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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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Cell Signaling in Plants01:25

Cell Signaling in Plants

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Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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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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Related Experiment Video

Updated: Oct 21, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Modeling Paracrine Noncanonical Wnt Signaling In Vitro

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LGR4: Not Just for Wnt Anymore?

Payton D Stevens1, Bart O Williams2

  • 1Van Andel Institute, Grand Rapids, Michigan.

Cancer Research
|September 2, 2021
PubMed
Summary

Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) has a newly discovered role in regulating EGF receptor signaling, independent of its known Wnt pathway function. This finding impacts our understanding of cancer signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is primarily known for its role in Wnt signaling, acting as a receptor for R-spondins and modulating Frizzled (FZD) receptor levels.
  • This interaction with RNF43 and ZNRF3 ubiquitin ligases leads to FZD ubiquitination, reducing Wnt pathway activation.
  • Previous understanding predominantly focused on LGR4's Wnt-dependent functions, with limited exploration of alternative roles.

Purpose of the Study:

  • To investigate the non-Wnt-dependent functions of LGR4, particularly its potential role in other signaling pathways relevant to cancer.
  • To explore the correlation between LGR4 expression and signaling pathways beyond the Wnt pathway in breast tumors.
  • To elucidate the molecular mechanisms by which LGR4 might regulate other receptor tyrosine kinases.

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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
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The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions

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Last Updated: Oct 21, 2025

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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
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Main Methods:

  • Analysis of LGR4 expression levels in breast tumors and correlation with Wnt-associated gene signatures and Epidermal Growth Factor Receptor (EGFR) signaling.
  • Experimental manipulation of LGR4 expression to assess its impact on EGFR signaling.
  • Co-immunoprecipitation assays to investigate the physical interaction between LGR4, EGFR, and ubiquitin ligases.

Main Results:

  • High LGR4 expression in breast tumors correlated with poor patient outcomes and strongly with EGFR signaling, but not with Wnt-associated gene signatures.
  • Reduced LGR4 expression inhibited EGFR signaling, suggesting a regulatory role.
  • LGR4 was found to co-immunoprecipitate with EGFR and inhibit EGFR ubiquitination, potentially via the Casitas B-lineage lymphoma ubiquitin E3 ligase.

Conclusions:

  • LGR4 plays a significant role in regulating EGFR signaling, independent of its established function in the Wnt pathway.
  • This discovery challenges the Wnt-centric view of LGR4 and highlights its dual role in cancer signaling.
  • The findings suggest novel therapeutic strategies targeting LGR4 in cancers driven by EGFR signaling.