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MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic...

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Autores principales: Kong, Xiangjun, Li, Gaopeng, Yuan, Yan, He, Yan, Wu, Xiaoli, Zhang, Weijie, Wu, Zhengsheng, Chen, Tingting, Wu, Wenyong, Lobie, Peter E., Zhu, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410899/
https://www.ncbi.nlm.nih.gov/pubmed/22876288
http://dx.doi.org/10.1371/journal.pone.0041523
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author Kong, Xiangjun
Li, Gaopeng
Yuan, Yan
He, Yan
Wu, Xiaoli
Zhang, Weijie
Wu, Zhengsheng
Chen, Tingting
Wu, Wenyong
Lobie, Peter E.
Zhu, Tao
author_facet Kong, Xiangjun
Li, Gaopeng
Yuan, Yan
He, Yan
Wu, Xiaoli
Zhang, Weijie
Wu, Zhengsheng
Chen, Tingting
Wu, Wenyong
Lobie, Peter E.
Zhu, Tao
author_sort Kong, Xiangjun
collection PubMed
description Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression.
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spelling pubmed-34108992012-08-08 MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression Kong, Xiangjun Li, Gaopeng Yuan, Yan He, Yan Wu, Xiaoli Zhang, Weijie Wu, Zhengsheng Chen, Tingting Wu, Wenyong Lobie, Peter E. Zhu, Tao PLoS One Research Article Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression. Public Library of Science 2012-08-02 /pmc/articles/PMC3410899/ /pubmed/22876288 http://dx.doi.org/10.1371/journal.pone.0041523 Text en © 2012 Kong 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
Kong, Xiangjun
Li, Gaopeng
Yuan, Yan
He, Yan
Wu, Xiaoli
Zhang, Weijie
Wu, Zhengsheng
Chen, Tingting
Wu, Wenyong
Lobie, Peter E.
Zhu, Tao
MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title_full MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title_fullStr MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title_full_unstemmed MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title_short MicroRNA-7 Inhibits Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer Cells via Targeting FAK Expression
title_sort microrna-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting fak expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410899/
https://www.ncbi.nlm.nih.gov/pubmed/22876288
http://dx.doi.org/10.1371/journal.pone.0041523
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