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BMP-2 induces EMT and breast cancer stemness through Rb and CD44

Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms unde...

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Autores principales: Huang, Peide, Chen, Anan, He, Weiyi, Li, Zhen, Zhang, Guanglin, Liu, Zhong, Liu, Ge, Liu, Xueting, He, Shuilian, Xiao, Gang, Huang, Feicheng, Stenvang, Jan, Brünner, Nils, Hong, An, Wang, Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511860/
https://www.ncbi.nlm.nih.gov/pubmed/28725489
http://dx.doi.org/10.1038/cddiscovery.2017.39
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author Huang, Peide
Chen, Anan
He, Weiyi
Li, Zhen
Zhang, Guanglin
Liu, Zhong
Liu, Ge
Liu, Xueting
He, Shuilian
Xiao, Gang
Huang, Feicheng
Stenvang, Jan
Brünner, Nils
Hong, An
Wang, Ju
author_facet Huang, Peide
Chen, Anan
He, Weiyi
Li, Zhen
Zhang, Guanglin
Liu, Zhong
Liu, Ge
Liu, Xueting
He, Shuilian
Xiao, Gang
Huang, Feicheng
Stenvang, Jan
Brünner, Nils
Hong, An
Wang, Ju
author_sort Huang, Peide
collection PubMed
description Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway. In addition, the Smad signaling pathways are implicated in upregulation of CD44 protein expression by BMP-2. It was suggested that cross-talk exists between Rb and CD44 signaling pathways, as recombinant human BMP-2 (rhBMP-2) was found to regulate CD44 expression partly through Rb signals. In clinical tissues, BMP-2 was positively and negatively correlated with CD44 and Rb expression, respectively. Based on the in vitro and in vivo results, we have established an integrated mechanism by which rhBMP-2 induces EMT and stemness of breast cancer cells via the Rb and CD44 signaling pathways, which then contribute to breast cancer metastasis. These findings may be helpful for developing new strategies for the treatment and prognosis of advanced breast cancer.
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spelling pubmed-55118602017-07-19 BMP-2 induces EMT and breast cancer stemness through Rb and CD44 Huang, Peide Chen, Anan He, Weiyi Li, Zhen Zhang, Guanglin Liu, Zhong Liu, Ge Liu, Xueting He, Shuilian Xiao, Gang Huang, Feicheng Stenvang, Jan Brünner, Nils Hong, An Wang, Ju Cell Death Discov Article Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway. In addition, the Smad signaling pathways are implicated in upregulation of CD44 protein expression by BMP-2. It was suggested that cross-talk exists between Rb and CD44 signaling pathways, as recombinant human BMP-2 (rhBMP-2) was found to regulate CD44 expression partly through Rb signals. In clinical tissues, BMP-2 was positively and negatively correlated with CD44 and Rb expression, respectively. Based on the in vitro and in vivo results, we have established an integrated mechanism by which rhBMP-2 induces EMT and stemness of breast cancer cells via the Rb and CD44 signaling pathways, which then contribute to breast cancer metastasis. These findings may be helpful for developing new strategies for the treatment and prognosis of advanced breast cancer. Nature Publishing Group 2017-07-17 /pmc/articles/PMC5511860/ /pubmed/28725489 http://dx.doi.org/10.1038/cddiscovery.2017.39 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Huang, Peide
Chen, Anan
He, Weiyi
Li, Zhen
Zhang, Guanglin
Liu, Zhong
Liu, Ge
Liu, Xueting
He, Shuilian
Xiao, Gang
Huang, Feicheng
Stenvang, Jan
Brünner, Nils
Hong, An
Wang, Ju
BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title_full BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title_fullStr BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title_full_unstemmed BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title_short BMP-2 induces EMT and breast cancer stemness through Rb and CD44
title_sort bmp-2 induces emt and breast cancer stemness through rb and cd44
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511860/
https://www.ncbi.nlm.nih.gov/pubmed/28725489
http://dx.doi.org/10.1038/cddiscovery.2017.39
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