title: Cellular microenvironment controls the nuclear architecture of breast epithelia through β1-integrin.
abstract: Defects in nuclear architecture occur in a variety of diseases, however the fundamental mechanisms that control the internal structure of nuclei are poorly defined. Here we reveal that the cellular microenvironment has a profound influence on the global internal organization of nuclei in breast epithelia. A 3D microenvironment induces a prolonged but reversible form of cell cycle arrest that features many of the classical markers of cell senescence. This unique form of arrest is dependent on signaling from the external microenvironment through β1-integrins. It is concomitant with alterations in nuclear architecture that characterize the withdrawal from cell proliferation. Unexpectedly, following prolonged cell cycle arrest in 3D, the senescence-like state and associated reprogramming of nuclear architecture are freely reversible on altering the dimensionality of the cellular microenvironment. Breast epithelia can therefore maintain a proliferative plasticity that correlates with nuclear remodelling. However, the changes in nuclear architecture are cell lineage-specific and do not occur in fibroblasts, and moreover they are overcome in breast cancer cells.
authors.affiliation: a Faculty of Life Sciences and Wellcome Trust Center for Cell-Matrix Research, University of Manchester , Manchester , United Kingdom.|b Department of Genome Integrity , Danish Cancer Society Research Center , Copenhagen , Denmark.
authors.forename: Apolinar
authors.initials: A
authors.lastname: Maya-Mendoza
authors.affiliation: b Department of Genome Integrity , Danish Cancer Society Research Center , Copenhagen , Denmark.|c Science for Life Laboratory, Division of Translational Medicine and Chemical Biology , Department of Medical Biochemistry and Biophysics, Karolinska Institute , Stockholm , Sweden.
authors.forename: Jiri
authors.initials: J
authors.lastname: Bartek
authors.affiliation: a Faculty of Life Sciences and Wellcome Trust Center for Cell-Matrix Research, University of Manchester , Manchester , United Kingdom.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Jackson
authors.affiliation: a Faculty of Life Sciences and Wellcome Trust Center for Cell-Matrix Research, University of Manchester , Manchester , United Kingdom.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Streuli
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D019012:Integrin beta1 / Q000378:metabolism*; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D018613:Microscopy, Confocal
chemical_list: D019012:Integrin beta1; D016590:Aphidicolin
keywords: breast cancer; breast mammary gland; cell cycle; cell senescence; extracellular matrix; integrin; nuclear structure
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