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Updated: Nov 19, 2025

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

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Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness

Jiongjia Cheng1, Masanao Tsuda2, Karl Okolotowicz1

  • 1Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.

Cell Chemical Biology
|January 27, 2021
PubMed

Insights

Wnt signaling regulates tissue renewal and cancer. New research reveals how stress pathways involving ATM, HIPK2, and p53 indirectly control Wnt target genes, impacting cell shape and renewal.

Area of Science:

  • Molecular biology
  • Cell signaling
  • Cancer research

Background:

  • Wnt signaling is crucial for tissue homeostasis and cancer development.
  • Beta-catenin activation of TCF/LEF transcription factors mediates Wnt signaling.
  • Coordination of Wnt signaling with tissue organization and renewal remains a key question.

Purpose of the Study:

  • To elucidate the molecular mechanisms linking cellular stress to Wnt signaling.
  • To investigate how stress signaling pathways modulate TCF/LEF transcriptional activity.
  • To understand the implications for tissue renewal and cancer therapeutics.

Main Methods:

  • Utilized a novel class of small molecules targeting tubulin.
  • Investigated the molecular cascade involving ATM, HIPK2, and p53.
  • Assessed the regulation of TCF/LEF transcriptional activity under stress conditions.

Main Results:

  • Identified a molecular cascade linking stress signaling (ATM, HIPK2, p53) to TCF/LEF activity.
  • Demonstrated that mitotic and genotoxic stress indirectly modulate Wnt responsiveness.
  • Observed coherent control over cell shape and renewal mediated by this stress-Wnt crosstalk.

Conclusions:

  • Stress signaling pathways provide an indirect mechanism to regulate Wnt target gene expression.
  • This crosstalk allows for coordinated control of cell shape and renewal in response to stress.
  • Findings offer insights into tissue morphogenesis and potential small-molecule anticancer drug development.
Keywords:
Aurora kinasesLEFTCFWntataxia telangiectasia mutated/ATMhomeodomain-interacting protein kinase/HIPK2p53β-catenin

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