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Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity

Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during meta...

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Autores principales: Jia, Rongjie, Liang, Yingchao, Chen, Rui, Liu, Guoke, Wang, Hao, Tang, Min, Zhou, Xuyu, Wang, Huajing, Yang, Yang, Wei, Huafeng, Li, Bohua, Song, Yipeng, Zhao, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5261026/
https://www.ncbi.nlm.nih.gov/pubmed/28032860
http://dx.doi.org/10.1038/cddis.2016.422
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author Jia, Rongjie
Liang, Yingchao
Chen, Rui
Liu, Guoke
Wang, Hao
Tang, Min
Zhou, Xuyu
Wang, Huajing
Yang, Yang
Wei, Huafeng
Li, Bohua
Song, Yipeng
Zhao, Jian
author_facet Jia, Rongjie
Liang, Yingchao
Chen, Rui
Liu, Guoke
Wang, Hao
Tang, Min
Zhou, Xuyu
Wang, Huajing
Yang, Yang
Wei, Huafeng
Li, Bohua
Song, Yipeng
Zhao, Jian
author_sort Jia, Rongjie
collection PubMed
description Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization. Unlike secretory OPN (sOPN), which triggers the epithelial–mesenchymal transition (EMT) to initiate cancer metastasis, intracellular/nuclear OPN (iOPN) induces the mesenchymal–epithelial transition (MET) to facilitate the formation of metastases. Nuclear OPN is found to interact with HIF2α and impact the subsequent AKT1/miR-429/ZEB cascade. In vivo assays confirm that the progression of metastatic colonization is accompanied by the nuclear accumulation of OPN and the MET process. Furthermore, evidence of nuclear OPN in the lung metastases is exhibited in clinical specimens. Finally, VEGF in the microenvironment was shown to induce the translocation of OPN into the nucleus through a KDR/PLCγ/PKC-dependent pathway. Taken together, our results describe the pleiotropic roles of OPN in the tumor metastasis cascade, which indicate its potential as an effective target for both early and advanced tumors.
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spelling pubmed-52610262017-01-26 Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity Jia, Rongjie Liang, Yingchao Chen, Rui Liu, Guoke Wang, Hao Tang, Min Zhou, Xuyu Wang, Huajing Yang, Yang Wei, Huafeng Li, Bohua Song, Yipeng Zhao, Jian Cell Death Dis Original Article Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization. Unlike secretory OPN (sOPN), which triggers the epithelial–mesenchymal transition (EMT) to initiate cancer metastasis, intracellular/nuclear OPN (iOPN) induces the mesenchymal–epithelial transition (MET) to facilitate the formation of metastases. Nuclear OPN is found to interact with HIF2α and impact the subsequent AKT1/miR-429/ZEB cascade. In vivo assays confirm that the progression of metastatic colonization is accompanied by the nuclear accumulation of OPN and the MET process. Furthermore, evidence of nuclear OPN in the lung metastases is exhibited in clinical specimens. Finally, VEGF in the microenvironment was shown to induce the translocation of OPN into the nucleus through a KDR/PLCγ/PKC-dependent pathway. Taken together, our results describe the pleiotropic roles of OPN in the tumor metastasis cascade, which indicate its potential as an effective target for both early and advanced tumors. Nature Publishing Group 2016-12 2016-12-29 /pmc/articles/PMC5261026/ /pubmed/28032860 http://dx.doi.org/10.1038/cddis.2016.422 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. 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 Original Article
Jia, Rongjie
Liang, Yingchao
Chen, Rui
Liu, Guoke
Wang, Hao
Tang, Min
Zhou, Xuyu
Wang, Huajing
Yang, Yang
Wei, Huafeng
Li, Bohua
Song, Yipeng
Zhao, Jian
Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title_full Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title_fullStr Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title_full_unstemmed Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title_short Osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
title_sort osteopontin facilitates tumor metastasis by regulating epithelial–mesenchymal plasticity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5261026/
https://www.ncbi.nlm.nih.gov/pubmed/28032860
http://dx.doi.org/10.1038/cddis.2016.422
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