A stiffness-gated YAP-β-catenin axis orchestrates AXIN2 expression in metastatic breast cancer.

Yuning Wu, Zhi Su, Chang Ge, Shumaim Barooj, Jeremy A Hirota, Fei Geng

Abstract read

In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yuning WuSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Zhi SuSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Chang GeSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Shumaim BaroojSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Jeremy A HirotaSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Fei GengSchool of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Breast cancer progression is strongly influenced by the mechanical properties of the tumor microenvironment, yet how extracellular matrix stiffness coordinates signaling between YAP and β-catenin remains unclear. Using breast cancer cells cultured on soft and stiff 2D substrates and 3D Matrigel spheroids, we show that the rigid matrices drive joint nuclear localization of YAP and β-catenin, whereas compliant environments reveal a compensatory increase in β-catenin nuclear entry following YAP depletion. However, this increase is insufficient to activate canonical Wnt targets, and AXIN2 emerges as a stiffness-sensitive gene requiring cooperative input from both regulators. Cytoskeletal tension and cell density further tune this interplay, indicating that mechanical and architectural cues jointly govern nuclear signaling. In 3D culture, YAP loss reduces β-catenin nuclear localization and spheroid viability in a stiffness-dependent manner. These findings identify a mechanically gated YAP-β-catenin axis that integrates multiple microenvironmental cues to shape transcriptional programs in metastatic breast cancer.

Indexed as

CancerCell biologyMechanobiology

Identifiers

PMID41536990

DOI10.1016/j.isci.2025.114405

PMCPMC12796759

What Socratic holds

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LicenceCC BY

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.