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

Apolinar Maya-Mendoza, J Bartek, Dean Jackson, Charles Streuli

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)345-356
Number of pages12
JournalCell Cycle
Volume15
Issue number3
Early online date28 Jan 2016
DOIs
Publication statusPublished - 2016

Keywords

  • Breast cancer
  • breast mammary gland
  • Cell Cycle
  • Cell senescence
  • Extracellular matrix
  • Integrin
  • Nuclear structure

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