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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 19, n. 10, p. 2102-2115, JUN 6 2017.
• Citações Web of Science: 14

Resumo

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. (AU)

• Processo FAPESP: 14/25832-1 - A via Hippo-YAP como mediadora de sinais bioquímicos da matriz extracelular em células epiteliais não-malignas e malignas da glândula mamária
• Beneficiário: Ana Paula Zen Petisco Fiore
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/50938-8 - INCT 2014: em Fotônica Aplicada à Biologia Celular INFABiC
• Beneficiário: Hernandes Faustino de Carvalho
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/10492-0 - Hippo-YAP como uma via de convergência dos sinais bioquímicos e mecânicos provenientes da matriz extracelular durante a morfogênese da glândula mamária e a progressão do câncer de mama
• Beneficiário: Alexandre Bruni Cardoso
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores