Cited by 46Wnt/β-catenin signaling in development and cancerCellular Mechanics and InteractionsHippo pathway signaling and YAP/TAZ

Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis

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Benham-Pyle, Blair W, Sim, Joo Yong, Hart, Kevin C, Pruitt, Beth L, Nelson, William James·2016·eLife

Abstract

Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division. We show that mechanical strain induced Src-dependent phosphorylation of Y654 β-catenin and increased β-catenin-mediated transcription in mammalian MDCK epithelial cells. Under these conditions, cells accumulated in S/G2 (independent of DNA damage) but did not divide. Activating β-catenin through Casein Kinase I inhibition or Wnt3A addition increased β-catenin-mediated transcription and strain-induced accumulation of cells in S/G2. Significantly, only the combination of mechanical strain and Wnt/β-catenin activation triggered cells in S/G2 to divide. These results indicate that strain-induced Src phosphorylation of β-catenin and Wnt-dependent β-catenin stabilization synergize to increase β-catenin-mediated transcription to levels required for mitosis. Thus, local Wnt signaling may fine-tune the effects of global mechanical strain to restrict cell divisions during tissue development and homeostasis.

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  • A role for Wnt signaling during M phase has been suggested based on high Wnt/β-catenin signaling activity during cell division.

    “A role for Wnt signaling during M phase has also been suggested based on high Wnt/β-catenin signaling activity during cell division, through an unknown mechanism (39, 40).”

    From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [40]

    The Discussion reports that higher Wnt3A/β-catenin activity drove mechanically strained cells from G2 into mitosis, supporting a suggested role in mitotic progression. It does not establish that signaling activity was high during M phase itself; the reported activity concerns progression into mitosis. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • High Wnt/βcatenin signaling activity during cell division suggests a link between Wnt signaling and mitosis.

    “High Wnt/βcatenin signaling activity during cell division has suggested a link between Wnt signaling and mitosis through unknown mechanisms (Benham-Pyle et al. 2016;Niehrs and Acebron 2012).”

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Benham-Pyle, B. W., Sim, J. Y., Hart, K. C., Pruitt, B. L., & Nelson, W. J.
Affiliations
  • Stanford University (US)
  • Stanford Cardiovascular Institute (US)
Corresponding author
Nelson, William James
Venue
eLife
Published
2016-10-26
Volume
5
ISSN
2050-084X (ISSN-L)
OpenAlex
W2541569086
Cited by
46
References
2
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 10 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 1
FWCI
2.43
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1136790, Graduate Student Fellowship, DGE-114747)
  • National Institutes of Health (T32GM007276, 11R35GM118064-01)
  • Stanford University (Bio-X Graduate Fellowship, Lieberman Graduate Fellowship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
β-catenin, Wnt3a, mechanical strain, cell cycle progression, mitosis, Src phosphorylation, casein kinase 1, β-catenin stabilization, Wnt/β-catenin signaling, mechanical forces, MDCK cells, tissue expansion
MeSH terms
Animals, Dogs, Mitosis, Phosphorylation, Protein Processing, Post-Translational, src-Family Kinases, beta Catenin, Mechanical Phenomena, Wnt Signaling Pathway, Wnt3A Protein, Madin Darby Canine Kidney Cells

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