Evidence map›Paper›PMID 41882003›Full record

ArticleNature communications2026

Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction.

Zhimin Hu, Hannah E Majeski, Aida Mestre-Farrera, Shirong Cai, Arya Lalezarzadeh, Yichi Zhang, Kei-Ichiro Arimoto, Dong-Er Zhang, Helen Piwnica-Worms, Laurent Fattet and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Zhimin Hu *Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-4997-0986
Hannah E Majeski *Department of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Aida Mestre-FarreraDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Shirong CaiDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Arya LalezarzadehDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0002-1986-7598
Yichi ZhangDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0009-0003-3726-7243
Kei-Ichiro ArimotoDepartment of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Dong-Er ZhangDepartment of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Helen Piwnica-WormsDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4210-6738
Laurent FattetDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5152-4937
Jing YangDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. jingyang@ucsd.edu.ORCID http://orcid.org/0000-0001-8410-3549

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
Regulation of Tumor Invasion and Metastasis by Matrix StiffnessR01CA174869 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jing Yang · 2015 to 2026
$4.3M
EPHA2 Receptor Signaling in Breast Cancer MechanotransductionR01CA262794 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE, Jing Yang · 2022 to 2026
$2.9M
Functional interplay between Hippo and estrogen receptor ESR1R01CA268179 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jing Yang · 2022 to 2026
$2.1M
Apical-basal polarity in tumor progression and metastasisR01CA236386 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YANG, JING · 2019 to 2023
$1.9M
The role of Tyk2 in Twist1-mediated EMT and metastasis in response to matrix stiffnessF31CA213800 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MAJESKI, HANNAH E · 2017 to 2019
$112k
Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP160710NCI NIH HHS R01 CA174869NCI NIH HHS R01 CA262794NCI NIH HHS R01 CA268179Tobacco-Related Disease Research Program (TRDRP) T32FT4922U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) F31CA213800U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA23100U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA174869U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA236386U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA268179U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) RO1CA262794U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007752
6 · The paper itself

Abstract

Mechanical cues from the extracellular matrix (ECM) regulate various cellular processes. In breast cancer, increased tumor stiffness is associated with elevated metastasis risks and poor survival. Here we report a unique role of the JAK family kinase TYK2 in suppressing breast cancer metastasis under low ECM stiffness. Genetic or pharmacological inhibition of TYK2 in mammary acini and patient-derived organoids leads to invasion at low stiffness by promoting Epithelial-Mesenchymal Transition, which is independent of cytokine-induced JAK/STAT signaling. TYK2 blockade promotes metastasis in breast tumor cell- and patient-derived xenografts. TYK2 localizes at the plasma membrane via IFNAR1 association under low ECM stiffness, whereas high rigidity causes TYK2 cytoplasmic mislocalization and inactivation. Consistently, normal breast epithelium displays membrane-localized TYK2, whereas invasive breast tumors exhibit cytoplasmic TYK2. These findings uncover a TYK2-dependent mechanism by which ECM rigidity suppresses breast cancer metastasis and underscore the need for breast cancer screening in patients receiving TYK2 inhibitors.

Indexed as

Breast NeoplasmsExtracellular MatrixMechanotransduction, CellularTYK2 KinaseAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleHumansMiceNeoplasm MetastasisSignal TransductionTYK2 KinaseTYK2 protein, human

Identifiers

PMID41882003
PMCPMC13181009

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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 OpenQuestion graph.