Cellular microenvironment controls the nuclear architecture of breast epithelia through β1-integrin

Cell Cycle
A Maya-MendozaC H Streuli

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.

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Citations

May 5, 2016·Breast Cancer Research : BCR·Michael J SherrattCharles H Streuli
Oct 1, 2016·Molecular Biology of the Cell·Charles H Streuli
Jul 8, 2017·Cancers·Elena MadrazoJavier Redondo-Muñoz
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Feb 3, 2019·Journal of Cell Science·Charles H Streuli, Qing-Jun Meng
Dec 24, 2019·Frontiers in Oncology·Sara Sofia Deville, Nils Cordes
Oct 24, 2018·Breast Cancer Research : BCR·Safiah OlabiCharles H Streuli
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Jan 29, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Fabian BaltesGerd Bendas
Jul 22, 2021·ACS Biomaterials Science & Engineering·Gowri Manohari BalachanderKaushik Chatterjee
Apr 4, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sophie A LelièvreShirisha Chittiboyina

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Methods Mentioned

BETA
confocal microscopy

Software Mentioned

ImarisTM
Image J
LSM

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