Evidence map›Paper›PMID 41279022›Full record

ArticlebioRxiv : the preprint server for biology2025

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 readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Zhimin HuDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Hannah E MajeskiDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Aida Mestre-FarreraDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Shirong CaiDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Arya LalezarzadehDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Yichi ZhangDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Kei-Ichiro ArimotoDepartment of Pathology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Dong-Er ZhangDepartment of Pathology and Department of Molecular Biology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Helen Piwnica-WormsDepartment of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Laurent FattetDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.
Jing YangDepartment of Pharmacology, Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0819, USA.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
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
NCI NIH HHS F31 CA213800NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA174869NCI NIH HHS R01 CA236386NCI NIH HHS R01 CA262794NCI NIH HHS R01 CA268179NIGMS NIH HHS T32 GM007752
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 risk and poor survival. We identify 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 ECM 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 stiffness, but it becomes cytoplasmic and inactivated at high stiffness. Normal human 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 vigilant breast cancer screening in patients receiving TYK2 inhibitors.

Identifiers

PMID41279022
PMCPMC12636551

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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.