Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.

Autor:	Munne PM; 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., Martikainen L; Department of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland., Räty I; 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., Bertula K; Department of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland., Nonappa; Department of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.; Department of Bioproducts and Biosystems, Aalto University School of Chemical Engineering, Espoo, Finland., Ruuska J; 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., Ala-Hongisto H; 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., Peura A; 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., Hollmann B; 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., Euro L; Research Program of Stem Cells and Metabolism, Biomedicum Helsinki, University of Helsinki, 00290, Helsinki, Finland., Yavuz K; Applied Tumor Genomics Research Program, Enhancer Biology Laboratory, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Patrikainen L; 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., Salmela M; 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., Pokki J; Department of Electrical Engineering and Automation, Aalto University, Espoo, Finland., Kivento M; Applied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland., Väänänen J; Applied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland., Suomi T; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland., Nevalaita L; 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., Mutka M; Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland., Kovanen P; Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland., Leidenius M; Breast Surgery Unit, Helsinki University Central Hospital, Helsinki, Finland., Meretoja T; Breast Surgery Unit, Helsinki University Central Hospital, Helsinki, Finland., Hukkinen K; Department of Mammography, Helsinki University Central Hospital, Helsinki, Finland., Monni O; Applied Tumor Genomics Research Program, Faculty of Medicine, Oncogenomics Laboratory, University of Helsinki, Helsinki, Finland., Pouwels J; 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., Sahu B; Applied Tumor Genomics Research Program, Enhancer Biology Laboratory, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Mattson J; Department of Oncology, University of Helsinki & Helsinki University Hospital, Helsinki, Finland., Joensuu H; Department of Oncology, University of Helsinki & Helsinki University Hospital, Helsinki, Finland., Heikkilä P; Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland., Elo LL; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520, Turku, Finland., Metcalfe C; Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA., Junttila MR; Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA., Ikkala O; Department of Applied Physics, Molecular Materials Group, Aalto University School of Science, PO Box, 15100, FI-00076, Espoo, Finland.; Department of Bioproducts and Biosystems, Aalto University School of Chemical Engineering, Espoo, Finland., Klefström J; 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. Juha.Klefstrom@helsinki.fi.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2021 Nov 29; Vol. 12 (1), pp. 6967. Date of Electronic Publication: 2021 Nov 29.
DOI:	10.1038/s41467-021-27220-9
Abstrakt:	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. (© 2021. The Author(s).)
Databáze:	MEDLINE
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