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Updated: Jul 15, 2025

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

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When You Come to a Fork in the Road, Take It: Wnt Signaling Activates Multiple Pathways through the APC/Axin/GSK-3

Chenchen Li1, Emma E Furth2, Anil K Rustgi3,4

  • 1Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cells
|September 28, 2023
PubMed

Insights

The Wnt signaling pathway regulates development and stem cells. This review explores alternative effectors, beyond beta-catenin, in canonical Wnt signaling that contribute to cancer development.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Oncology

Background:

  • The Wnt signaling pathway is crucial for metazoan development and stem cell maintenance.
  • Aberrant Wnt activation is a key event in various cancers.
  • The canonical Wnt pathway involves Wnt proteins, a receptor complex, and the APC/Axin/GSK-3 inhibitory complex.

Purpose of the Study:

  • To review alternative effectors of the canonical Wnt pathway.
  • To elucidate the role of these effectors in cancer.
  • To highlight Wnt signaling's multifaceted role in oncogenesis.

Main Methods:

  • Literature review of canonical Wnt pathway mechanisms.
  • Analysis of Wnt signaling's non-canonical effectors.
  • Integration of findings related to cancer biology.

Main Results:

  • Canonical Wnt signaling impacts effectors beyond beta-catenin.
  • These alternative effectors include mTOR, protein stability regulators, spindle orientation, and Hippo signaling.
  • Dysregulation of these alternative pathways contributes to cancer progression.

Conclusions:

  • Canonical Wnt signaling has diverse effectors impacting multiple cellular processes.
  • Targeting these alternative Wnt effectors may offer novel cancer therapies.
  • Understanding these pathways is vital for comprehending Wnt-driven malignancies.
Keywords:
AxinWntadenomatous polyposis coli (APC)beta-catenincancerglycogen synthase kinase 3 (GSK-3)mTOR

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