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YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment
Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537044/ https://www.ncbi.nlm.nih.gov/pubmed/25980435 |
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author | Gopal, Shashi K. Greening, David W. Mathias, Rommel A. Ji, Hong Rai, Alin Chen, Maoshan Zhu, Hong-Jian Simpson, Richard J. |
author_facet | Gopal, Shashi K. Greening, David W. Mathias, Rommel A. Ji, Hong Rai, Alin Chen, Maoshan Zhu, Hong-Jian Simpson, Richard J. |
author_sort | Gopal, Shashi K. |
collection | PubMed |
description | Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCK(YBX1) cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID mice did not form tumours. Critically, MDCK(YBX1) cells established viable tumour xenografts, and immuno-histochemical staining indicated murine vascularization by CD31+ endothelial cells. We analysed the total secretome (containing soluble and extracellular vesicles) of MDCK(YBX1) cells to investigate regulation of the tumour microenvironment. YBX1 expression elevated release of secreted factors known to enhance angiogenesis (TGF-β, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to MDCK cells. Importantly, treatment with MDCK(YBX1) cell-derived secretome increased recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic enhancer that can regulate tumour angiogenesis via release of secreted modulators into the extracellular microenvironment. |
format | Online Article Text |
id | pubmed-4537044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-45370442015-08-26 YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment Gopal, Shashi K. Greening, David W. Mathias, Rommel A. Ji, Hong Rai, Alin Chen, Maoshan Zhu, Hong-Jian Simpson, Richard J. Oncotarget Research Paper Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCK(YBX1) cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID mice did not form tumours. Critically, MDCK(YBX1) cells established viable tumour xenografts, and immuno-histochemical staining indicated murine vascularization by CD31+ endothelial cells. We analysed the total secretome (containing soluble and extracellular vesicles) of MDCK(YBX1) cells to investigate regulation of the tumour microenvironment. YBX1 expression elevated release of secreted factors known to enhance angiogenesis (TGF-β, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to MDCK cells. Importantly, treatment with MDCK(YBX1) cell-derived secretome increased recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic enhancer that can regulate tumour angiogenesis via release of secreted modulators into the extracellular microenvironment. Impact Journals LLC 2015-04-23 /pmc/articles/PMC4537044/ /pubmed/25980435 Text en Copyright: © 2015 Gopal et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Gopal, Shashi K. Greening, David W. Mathias, Rommel A. Ji, Hong Rai, Alin Chen, Maoshan Zhu, Hong-Jian Simpson, Richard J. YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title | YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title_full | YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title_fullStr | YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title_full_unstemmed | YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title_short | YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
title_sort | ybx1/yb-1 induces partial emt and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537044/ https://www.ncbi.nlm.nih.gov/pubmed/25980435 |
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