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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

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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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Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.

Sharon H Choi1, Elizabeth Pan1, Andrew Elliott2

  • 1University of California San Diego, San Diego, California.

Molecular Cancer Research : MCR
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Alterations in the Wnt signaling pathway (WSP) are common in prostate cancer, particularly in metastatic sites. WSP-activated tumors show distinct molecular features and an immunosuppressed microenvironment, suggesting potential therapeutic targets.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Wnt signaling pathway (WSP) alterations are implicated in prostate cancer progression and resistance to therapy.
  • Understanding WSP molecular landscape is crucial for developing targeted treatments.

Purpose of the Study:

  • To characterize molecular alterations in canonical and noncanonical WSP in a large prostate cancer cohort.
  • To investigate the prevalence and clinical relevance of WSP activation in primary and metastatic prostate cancer.

Main Methods:

  • Multi-institutional dataset of 4,138 prostate cancer patients undergoing genomic sequencing.
  • Identification of WSP-activated tumors based on specific gene mutations (CTNNB1, RSPO2, APC, RNF43).
  • Analysis of noncanonical WSP markers (ROR1, ROR2, WNT5) and tumor microenvironment (macrophages).

Main Results:

  • WSP activation was more frequent in metastatic (19.1%) than primary (10.1%) prostate cancer.
  • WSP-activated tumors showed increased SPOP mutations and higher canonical WSP activator expression.
  • Elevated ROR1 gene expression and M2 macrophage predominance were observed in WSP-activated tumors.

Conclusions:

  • WSP activation is a significant feature in prostate cancer, especially in metastatic disease.
  • WSP-activated tumors exhibit a distinct molecular profile and an immunosuppressed tumor microenvironment.
  • ROR1 upregulation suggests crosstalk between canonical and noncanonical WSP, offering potential therapeutic avenues.