Evidence mapPaperPMID 40468448Full record

ArticleCell communication and signaling : CCS2025

Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer.

Feifei Yan, Sara Göransson, Helene Olofsson, Christos Vogiatzakis, Anagha Acharekar, Staffan Strömblad

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. 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. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Feifei Yan *Department of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
Sara Göransson *Department of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
Helene OlofssonDepartment of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
Christos VogiatzakisDepartment of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
Anagha AcharekarDepartment of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden.
Staffan StrömbladDepartment of Medicine Huddinge, Karolinska Institutet, Huddinge, SE-141 83, Sweden. staffan.stromblad@ki.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ductal carcinoma in situ (DCIS) is not life threatening unless it transitions into invasive breast cancer (IBC). However, although breast cancer cell exposure to matrix stiffening in vitro phenotypically mimics the DCIS to IBC switch, the molecular changes driving this switch remains unclear. Here, breast cancer cell kinome activity profiling suggested matrix stiffness-upregulation of 53 kinases, among which 16 kinases were also regulated by integrin β1. Functional validation identified matrix stiffness-activation of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) and mitogen-activated protein kinase 8 (MAPK8) signaling as critical for the stiffness-driven IBC phenotype, including for cell proliferation. The IKBKE-inhibitor Amlexanox, clinically utilized for aphthous ulcers, as well as the MAPK8 inhibitor JNK-IN-8, reinstalled the DCIS-like phenotype of breast cancer cells on high matrix stiffness. This suggests that IKBKE and/or MAPK8 inhibitors could enhance the arsenal of treatments to prevent or treat breast cancer.

Indexed as

Breast NeoplasmsCarcinoma, Intraductal, NoninfiltratingExtracellular MatrixI-kappa B KinaseSignal TransductionCell Line, TumorCell ProliferationFemaleHumansNeoplasm InvasivenessPhenotypeI-kappa B KinaseIKBKE protein, humanCellular signalingIntegrinKinaseKinomeMechanotransduction

Identifiers

PMID40468448
PMCPMC12139146

What Socratic holds

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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.