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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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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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WNT Signaling in Hematological Malignancies.

Michela Frenquelli1,2, Giovanni Tonon2,3

  • 1B-cell Neoplasia Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Frontiers in Oncology
|January 7, 2021
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Summary

The WNT signaling pathway regulates cell functions and is often deregulated in blood cancers. Aberrant WNT activation in hematological malignancies presents a potential therapeutic target.

Keywords:
ROR2WNTWnt/b-cateninmicroenvironmentmultiple myeloma

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Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The WNT signaling pathway is crucial for cellular processes like proliferation, differentiation, and migration.
  • WNT signaling involves ligands interacting with Frizzled, ROR1/ROR2, and RYK receptors, activating canonical (β-catenin dependent) or non-canonical pathways.
  • Aberrant WNT signaling, evidenced by high ligand and receptor expression in tumors, suggests its role in cancer progression and tumor microenvironment interactions.

Purpose of the Study:

  • To review the deregulation of WNT signaling pathways in hematological cancers.
  • To examine both ligand and receptor levels of WNT pathway involvement in these cancers.
  • To explore the therapeutic potential of targeting aberrant WNT activation in hematological malignancies.

Main Methods:

  • Literature review of WNT pathway deregulation in hematological cancers.
  • Analysis of both canonical (β-catenin dependent) and non-canonical WNT pathways.
  • Evaluation of preclinical data supporting WNT pathway as a therapeutic target.

Main Results:

  • WNT signaling pathways are frequently deregulated in hematological cancers at both ligand and receptor levels.
  • Both canonical and non-canonical WNT pathways are implicated in the pathogenesis of these cancers.
  • Preclinical evidence supports the potential of targeting WNT signaling for therapeutic benefit.

Conclusions:

  • WNT pathway dysregulation is a significant factor in hematological cancers.
  • Targeting WNT signaling, including its aberrant activation, offers a promising therapeutic strategy.
  • Further research into WNT pathway modulation could lead to novel treatments for blood cancers.