Cargando…
Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis
Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herei...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031464/ https://www.ncbi.nlm.nih.gov/pubmed/21148292 http://dx.doi.org/10.1091/mbc.e10-09-0790 |
_version_ | 1782197344367804416 |
---|---|
author | Deakin, Nicholas O. Turner, Christopher E. |
author_facet | Deakin, Nicholas O. Turner, Christopher E. |
author_sort | Deakin, Nicholas O. |
collection | PubMed |
description | Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herein we show that the focal adhesion adaptor protein, paxillin, and the closely related Hic-5 have distinct and unique roles in the regulation of breast cancer cell lung metastasis by modulating cell morphology and cell invasion through three-dimensional extracellular matrices (3D ECMs). Cells depleted of paxillin by RNA interference displayed a highly elongated mesenchymal morphology, whereas Hic-5 knockdown induced an amoeboid phenotype with both cell populations exhibiting reduced plasticity, migration persistence, and velocity through 3D ECM environments. In evaluating associated signaling pathways, we determined that Rac1 activity was increased in cells devoid of paxillin whereas Hic-5 silencing resulted in elevated RhoA activity and associated Rho kinase–induced nonmuscle myosin II activity. Hic-5 was essential for adhesion formation in 3D ECMs, and analysis of adhesion dynamics and lifetime identified paxillin as a key regulator of 3D adhesion assembly, stabilization, and disassembly. |
format | Text |
id | pubmed-3031464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30314642011-04-16 Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis Deakin, Nicholas O. Turner, Christopher E. Mol Biol Cell Articles Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herein we show that the focal adhesion adaptor protein, paxillin, and the closely related Hic-5 have distinct and unique roles in the regulation of breast cancer cell lung metastasis by modulating cell morphology and cell invasion through three-dimensional extracellular matrices (3D ECMs). Cells depleted of paxillin by RNA interference displayed a highly elongated mesenchymal morphology, whereas Hic-5 knockdown induced an amoeboid phenotype with both cell populations exhibiting reduced plasticity, migration persistence, and velocity through 3D ECM environments. In evaluating associated signaling pathways, we determined that Rac1 activity was increased in cells devoid of paxillin whereas Hic-5 silencing resulted in elevated RhoA activity and associated Rho kinase–induced nonmuscle myosin II activity. Hic-5 was essential for adhesion formation in 3D ECMs, and analysis of adhesion dynamics and lifetime identified paxillin as a key regulator of 3D adhesion assembly, stabilization, and disassembly. The American Society for Cell Biology 2011-02-01 /pmc/articles/PMC3031464/ /pubmed/21148292 http://dx.doi.org/10.1091/mbc.e10-09-0790 Text en © 2011 Deakin and Turner. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Deakin, Nicholas O. Turner, Christopher E. Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title | Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title_full | Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title_fullStr | Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title_full_unstemmed | Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title_short | Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
title_sort | distinct roles for paxillin and hic-5 in regulating breast cancer cell morphology, invasion, and metastasis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031464/ https://www.ncbi.nlm.nih.gov/pubmed/21148292 http://dx.doi.org/10.1091/mbc.e10-09-0790 |
work_keys_str_mv | AT deakinnicholaso distinctrolesforpaxillinandhic5inregulatingbreastcancercellmorphologyinvasionandmetastasis AT turnerchristophere distinctrolesforpaxillinandhic5inregulatingbreastcancercellmorphologyinvasionandmetastasis |