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Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2

Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated...

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Autores principales: Smith, Bethany N., Burton, Liza J., Henderson, Veronica, Randle, Diandra D., Morton, Derrick J., Smith, Basil A., Taliaferro-Smith, Latonia, Nagappan, Peri, Yates, Clayton, Zayzafoon, Majd, Chung, Leland W. K., Odero-Marah, Valerie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133359/
https://www.ncbi.nlm.nih.gov/pubmed/25122124
http://dx.doi.org/10.1371/journal.pone.0104987
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author Smith, Bethany N.
Burton, Liza J.
Henderson, Veronica
Randle, Diandra D.
Morton, Derrick J.
Smith, Basil A.
Taliaferro-Smith, Latonia
Nagappan, Peri
Yates, Clayton
Zayzafoon, Majd
Chung, Leland W. K.
Odero-Marah, Valerie A.
author_facet Smith, Bethany N.
Burton, Liza J.
Henderson, Veronica
Randle, Diandra D.
Morton, Derrick J.
Smith, Basil A.
Taliaferro-Smith, Latonia
Nagappan, Peri
Yates, Clayton
Zayzafoon, Majd
Chung, Leland W. K.
Odero-Marah, Valerie A.
author_sort Smith, Bethany N.
collection PubMed
description Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2 by Snail in breast cancer cells. ERK1/2 activity (p-ERK) was higher in breast cancer patient tissue as compared to normal tissue. Snail and p-ERK were increased in several breast cancer cell lines as compared to normal mammary epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm. Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell migration, decreased cell adhesion and also increased tumorigenicity. Snail induced nuclear translocation of p-ERK, and the activation of its subcellular downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as shown by decreased Snail and vimentin expression, decreased cell migration and increased cell adhesion. Overall, our data suggest that ERK2 isoform activation by Snail in aggressive breast cancer cells leads to EMT associated with increased cell migration and decreased cell adhesion. This regulation is enhanced by positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting of ERK2 isoform may be beneficial for breast cancer.
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spelling pubmed-41333592014-08-19 Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2 Smith, Bethany N. Burton, Liza J. Henderson, Veronica Randle, Diandra D. Morton, Derrick J. Smith, Basil A. Taliaferro-Smith, Latonia Nagappan, Peri Yates, Clayton Zayzafoon, Majd Chung, Leland W. K. Odero-Marah, Valerie A. PLoS One Research Article Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2 by Snail in breast cancer cells. ERK1/2 activity (p-ERK) was higher in breast cancer patient tissue as compared to normal tissue. Snail and p-ERK were increased in several breast cancer cell lines as compared to normal mammary epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm. Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell migration, decreased cell adhesion and also increased tumorigenicity. Snail induced nuclear translocation of p-ERK, and the activation of its subcellular downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as shown by decreased Snail and vimentin expression, decreased cell migration and increased cell adhesion. Overall, our data suggest that ERK2 isoform activation by Snail in aggressive breast cancer cells leads to EMT associated with increased cell migration and decreased cell adhesion. This regulation is enhanced by positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting of ERK2 isoform may be beneficial for breast cancer. Public Library of Science 2014-08-14 /pmc/articles/PMC4133359/ /pubmed/25122124 http://dx.doi.org/10.1371/journal.pone.0104987 Text en © 2014 Smith et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Smith, Bethany N.
Burton, Liza J.
Henderson, Veronica
Randle, Diandra D.
Morton, Derrick J.
Smith, Basil A.
Taliaferro-Smith, Latonia
Nagappan, Peri
Yates, Clayton
Zayzafoon, Majd
Chung, Leland W. K.
Odero-Marah, Valerie A.
Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title_full Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title_fullStr Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title_full_unstemmed Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title_short Snail Promotes Epithelial Mesenchymal Transition in Breast Cancer Cells in Part via Activation of Nuclear ERK2
title_sort snail promotes epithelial mesenchymal transition in breast cancer cells in part via activation of nuclear erk2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133359/
https://www.ncbi.nlm.nih.gov/pubmed/25122124
http://dx.doi.org/10.1371/journal.pone.0104987
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