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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

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, invadopodia can...
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Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon towards...

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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression.

Zhe Jin1, Chenghai Zhao, Xiaorui Han

  • 1Department of Orthopedics, The First Hospital of China Medical University, Shenyang, China. jinzhecmu@yahoo.cn

BMC Cancer
|October 19, 2012
PubMed
Summary

Wnt5a promotes Ewing sarcoma (ES) metastasis by increasing CXCR4 expression when the Wnt antagonist SFRP5 is absent. This suggests Wnt5a overexpression and SFRP5 deficiency together drive ES metastasis.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Ewing sarcoma (ES) is a pediatric cancer with poor prognosis due to early metastasis.
  • Molecular mechanisms driving ES metastasis are not well understood.
  • Wnt5a is investigated as a potential pro-metastatic factor in ES.

Purpose of the Study:

  • To investigate the role of Wnt5a in Ewing sarcoma metastasis.
  • To explore the relationship between Wnt5a, CXCR4, and SFRP5 in ES.
  • To elucidate the molecular pathways involved in ES cell migration.

Main Methods:

  • Real-time PCR and Western blot to assess Wnt5a and CXCR4 expression in ES specimens and cell lines.
  • Analysis of Wnt antagonists (SFRP1, SFRP2, SFRP5) and noncanonical Wnt pathway components (p-JNK, p-cJUN).
  • Methylation-specific PCR (MSP) for SFRP gene silencing, Wnt5a knockdown, and SFRP5 overexpression experiments.

Main Results:

  • Wnt5a expression correlated positively with CXCR4 expression in ES.
  • Higher Wnt5a and CXCR4 levels were observed in metastatic ES patient specimens.
  • Wnt5a enhanced ES cell migration via CXCR4 upregulation; SFRP5 deficiency and Wnt5a overexpression promoted metastasis.
  • Wnt5a and SFRP5 modulated JNK/cJUN signaling pathways.

Conclusions:

  • Wnt5a promotes ES cell migration by upregulating CXCR4.
  • The absence of Wnt antagonist SFRP5 is crucial for Wnt5a-mediated metastasis.
  • Wnt5a overexpression and SFRP5 deficiency may act synergistically to drive Ewing sarcoma metastasis.