ArticleNature communications2021
Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
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31 citing papers in PubMed, 44 citations in OpenAlex.
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Embryonic scaling: morphogen gradients, size sensing, and scaler genes.Frontiers in cell and developmental biology · 2026Review
- Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses.Oncoimmunology · 2025Article
- The mechanoresponsive chromosomal passenger complex sustains furrow ingression under confinement.Journal of molecular cell biology · 2025Article
- Review
- Nanofibrillar Cellulose Hydrogels with Anionic Surface Modifications for Modulating Macrophage Phenotype in 3D Culture.ACS applied materials & interfaces · 2025Article
- Estrogen attenuates stiffness-driven fibrotic signaling via transcriptional regulation.Biophysical journal · 2025Article
- Soft matrix promotes immunosuppression in tumor-resident immune cells via COX-FGF2 signaling.Nature communications · 2025Article
- Anticancer Potential of Prebiotics: Targeting Estrogen Receptors and PI3K/AKT/mTOR in Breast Cancer.Biomedicines · 2025Review
- Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer.NAR cancer · 2025Article
- Patient-derived response estimates from zero-passage organoids of luminal breast cancer.Breast cancer research : BCR · 2024Article
- A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion.Nature communications · 2024Article
- A novel preclinical model of the normal human breast.Journal of mammary gland biology and neoplasia · 2024Article
- Respiratory complex I regulates dendritic cell maturation in explant model of human tumor immune microenvironment.Journal for immunotherapy of cancer · 2024Article
- Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke.PNAS nexus · 2024Article
- Identifying the effectiveness of 3D culture systems to recapitulate breast tumor tissue in situ.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Patient-derived response estimates from zero-passage organoids of luminal breast cancer.bioRxiv : the preprint server for biology · 2024Article
- Outlook and opportunities for engineered environments of breast cancer dormancy.Science advances · 2024Review
- Hepsin promotes breast tumor growth signaling via the TGFβ-EGFR axis.Molecular oncology · 2024Article
- A Decision Tree to Guide Human and Mouse Mammary Organoid Model Selection.Methods in molecular biology (Clifton, N.J.) · 2024Article
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Authors and funding
34 authors at 4 institutions in 1 country.
Pauliina M MunneFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-9720-9964
Lahja Martikainen *Department of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.ORCID http://orcid.org/0000-0002-7092-8467
Iiris Räty *Finnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-5241-1368
Kia BertulaDepartment of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.ORCID http://orcid.org/0000-0002-7134-3591
NonappaDepartment of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.ORCID http://orcid.org/0000-0002-6804-4128
Janika RuuskaFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-3978-2033
Hanna Ala-HongistoFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-5850-1623
Aino PeuraFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-8958-940X
Babette HollmannFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.
Lilya EuroResearch Program of Stem Cells and Metabolism, Biomedicum Helsinki, University of Helsinki, 00290, Helsinki, Finland.ORCID http://orcid.org/0000-0001-9705-3886
Kerim YavuzApplied Tumor Genomics Research Program, Enhancer Biology Laboratory, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-4980-8804
Linda PatrikainenFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.
Maria SalmelaFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.
Juho PokkiDepartment of Electrical Engineering and Automation, Aalto University, Espoo, Finland.ORCID http://orcid.org/0000-0002-3198-7675
Mikko KiventoApplied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-2188-0652
Juho VäänänenApplied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-8857-1411
Tomi SuomiTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland.ORCID http://orcid.org/0000-0003-3639-979X
Liina NevalaitaFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-3752-1873
Minna MutkaDepartment of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-8380-7293
Panu KovanenDepartment of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-8218-2271
Marjut LeideniusBreast Surgery Unit, Helsinki University Central Hospital, Helsinki, Finland.
Tuomo MeretojaBreast Surgery Unit, Helsinki University Central Hospital, Helsinki, Finland.
Katja HukkinenDepartment of Mammography, Helsinki University Central Hospital, Helsinki, Finland.
Outi MonniApplied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-2319-8799
Jeroen PouwelsFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland.
Biswajyoti SahuApplied Tumor Genomics Research Program, Enhancer Biology Laboratory, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-6576-5440
Johanna MattsonDepartment of Oncology, University of Helsinki & Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0002-9719-9110
Heikki JoensuuDepartment of Oncology, University of Helsinki & Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0003-0281-2507
Päivi HeikkiläDepartment of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Laura L EloTurku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland.ORCID http://orcid.org/0000-0001-5648-4532
Ciara MetcalfeGenentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Melissa R JunttilaGenentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Olli IkkalaDepartment of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.ORCID http://orcid.org/0000-0002-0470-1889
Juha KlefströmFinnish Cancer Institute, FICAN South Helsinki University Hospital & Translational Cancer Medicine, Medical Faculty, University of Helsinki. Cancer Cell Circuitry Laboratory, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland. Juha.Klefstrom@helsinki.fi.ORCID http://orcid.org/0000-0001-7124-8431
University of Helsinki · FIAalto University · FIHelsinki University Hospital · FIÅbo Akademi University · FI
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is now globally the most frequent cancer and leading cause of women's death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.
Indexed as
TranscriptomeBreast NeoplasmsCase-Control StudiesCell Line, TumorCinnamatesCollagenDrug CombinationsEnhancer of Zeste Homolog 2 ProteinEstradiolEstrogen Receptor alphaFemaleFulvestrantGene Expression ProfilingGene Expression Regulation, NeoplasticHistonesHumans3-(4-(2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acidCinnamatesCollagenDrug CombinationsEnhancer of Zeste Homolog 2 ProteinESR1 protein, humanEstradiolEstrogen Receptor alphaEZH2 protein, humanFulvestrantHistonesIndazolesLamininmatrigelp38 Mitogen-Activated Protein KinasesProteoglycansTamoxifen
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