Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-06-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717307076 |
| _version_ | 1818129748214153216 |
|---|---|
| author | Ana Paula Zen Petisco Fiore Virginia A. Spencer Hidetoshi Mori Hernandes F. Carvalho Mina J. Bissell Alexandre Bruni-Cardoso |
| author_facet | Ana Paula Zen Petisco Fiore Virginia A. Spencer Hidetoshi Mori Hernandes F. Carvalho Mina J. Bissell Alexandre Bruni-Cardoso |
| author_sort | Ana Paula Zen Petisco Fiore |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T07:54:04Z |
| format | Article |
| id | doaj.art-6e67de02ed454b62a9814af031d58cf1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T07:54:04Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6e67de02ed454b62a9814af031d58cf12022-12-22T01:15:15ZengElsevierCell Reports2211-12472017-06-0119102102211510.1016/j.celrep.2017.05.050Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6Ana Paula Zen Petisco Fiore0Virginia A. Spencer1Hidetoshi Mori2Hernandes F. Carvalho3Mina J. Bissell4Alexandre Bruni-Cardoso5Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilThermo Fisher Scientific, Frederick, MD 21703, USALife Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USAINFABiC – National Institute of Science and Technology on Photonics Applied to Cell Biology, Campinas, SP 13083-862, BrazilLife Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USADepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilNuclear 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.http://www.sciencedirect.com/science/article/pii/S2211124717307076nuclear actinlaminin-111exportin-6quiescenceextracellular matrixmammary glandbreast cancerbasement membrane |
| spellingShingle | Ana Paula Zen Petisco Fiore Virginia A. Spencer Hidetoshi Mori Hernandes F. Carvalho Mina J. Bissell Alexandre Bruni-Cardoso Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 Cell Reports nuclear actin laminin-111 exportin-6 quiescence extracellular matrix mammary gland breast cancer basement membrane |
| title | Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 |
| title_full | Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 |
| title_fullStr | Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 |
| title_full_unstemmed | Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 |
| title_short | Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6 |
| title_sort | laminin 111 and the level of nuclear actin regulate epithelial quiescence via exportin 6 |
| topic | nuclear actin laminin-111 exportin-6 quiescence extracellular matrix mammary gland breast cancer basement membrane |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717307076 |
| work_keys_str_mv | AT anapaulazenpetiscofiore laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 AT virginiaaspencer laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 AT hidetoshimori laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 AT hernandesfcarvalho laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 AT minajbissell laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 AT alexandrebrunicardoso laminin111andthelevelofnuclearactinregulateepithelialquiescenceviaexportin6 |