Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6

Ana Paula Zen Petisco Fiore, Virginia A. Spencer, Hidetoshi Mori, Hernandes F. Carvalho, Mina J. Bissell, Alexandre Bruni-Cardoso

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Nuclear actin (N-actin) is known to participate in the regulation of gene expression. We showed previously that N-actin levels mediate the growth and quiescence of mouse epithelial cells in response to laminin-111 (LN1), a component of the mammary basement membrane (BM). We know that BM is defective in malignant cells, and we show here that it is the LN1/N-actin pathway that is aberrant in human breast cancer cells, leading to continuous growth. Photobleaching assays revealed that N-actin exit in nonmalignant cells begins as early as 30 min after LN1 treatment. LN1 attenuates the PI3K pathway leading to upregulation of exportin-6 (XPO6) activity and shuttles actin out of the nucleus. Silencing XPO6 prevents quiescence. Malignant cells are impervious to LN1 signaling. These results shed light on the crucial role of LN1 in quiescence and differentiation and how defects in the LN1/PI3K/XPO6/N-actin axis explain the loss of tissue homeostasis and growth control that contributes to malignant progression.

Original languageEnglish (US)
Pages (from-to)2102-2115
Number of pages14
JournalCell Reports
Volume19
Issue number10
DOIs
StatePublished - Jun 6 2017

Keywords

  • basement membrane
  • breast cancer
  • exportin-6
  • extracellular matrix
  • laminin-111
  • mammary gland
  • nuclear actin
  • quiescence

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Fiore, A. P. Z. P., Spencer, V. A., Mori, H., Carvalho, H. F., Bissell, M. J., & Bruni-Cardoso, A. (2017). Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6. Cell Reports, 19(10), 2102-2115. https://doi.org/10.1016/j.celrep.2017.05.050