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Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer
Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-act...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491648/ https://www.ncbi.nlm.nih.gov/pubmed/31040369 http://dx.doi.org/10.1038/s41598-019-43261-z |
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author | Yoriki, Kaori Mori, Taisuke Kokabu, Tetsuya Matsushima, Hiroshi Umemura, Shiori Tarumi, Yosuke Kitawaki, Jo |
author_facet | Yoriki, Kaori Mori, Taisuke Kokabu, Tetsuya Matsushima, Hiroshi Umemura, Shiori Tarumi, Yosuke Kitawaki, Jo |
author_sort | Yoriki, Kaori |
collection | PubMed |
description | Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines, Ishikawa and HEC-1A, transfected with ERRα/PGC-1α expression plasmids or silenced for ERRα expression, were co-cultured with telomerase-transformed human endometrial stromal cells (T-HESCs). We found that EMT-associated factors including vimentin, Snail, and zinc finger E-box binding homeobox 1 were upregulated in cancer cells overexpressing ERRα/PGC-1α and that transforming growth factor-beta (TGF-β) was induced in T-HESCs in the same conditions. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-β in T-HESCs. ERRα/PGC-1α overexpression increased the expression of EMT-associated factors after TGF-β exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-β, whereas E-cadherin remained unchanged. Matrigel invasion assays revealed that ERRα knockdown attenuated the stimulation of migration and invasion by TGF-β. These findings suggest that ERRα is a potential target for inhibiting TGF-β-induced EMT through cancer-stromal interactions in endometrial cancer. |
format | Online Article Text |
id | pubmed-6491648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64916482019-05-17 Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer Yoriki, Kaori Mori, Taisuke Kokabu, Tetsuya Matsushima, Hiroshi Umemura, Shiori Tarumi, Yosuke Kitawaki, Jo Sci Rep Article Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines, Ishikawa and HEC-1A, transfected with ERRα/PGC-1α expression plasmids or silenced for ERRα expression, were co-cultured with telomerase-transformed human endometrial stromal cells (T-HESCs). We found that EMT-associated factors including vimentin, Snail, and zinc finger E-box binding homeobox 1 were upregulated in cancer cells overexpressing ERRα/PGC-1α and that transforming growth factor-beta (TGF-β) was induced in T-HESCs in the same conditions. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-β in T-HESCs. ERRα/PGC-1α overexpression increased the expression of EMT-associated factors after TGF-β exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-β, whereas E-cadherin remained unchanged. Matrigel invasion assays revealed that ERRα knockdown attenuated the stimulation of migration and invasion by TGF-β. These findings suggest that ERRα is a potential target for inhibiting TGF-β-induced EMT through cancer-stromal interactions in endometrial cancer. Nature Publishing Group UK 2019-04-30 /pmc/articles/PMC6491648/ /pubmed/31040369 http://dx.doi.org/10.1038/s41598-019-43261-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yoriki, Kaori Mori, Taisuke Kokabu, Tetsuya Matsushima, Hiroshi Umemura, Shiori Tarumi, Yosuke Kitawaki, Jo Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title | Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title_full | Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title_fullStr | Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title_full_unstemmed | Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title_short | Estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
title_sort | estrogen-related receptor alpha induces epithelial-mesenchymal transition through cancer-stromal interactions in endometrial cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491648/ https://www.ncbi.nlm.nih.gov/pubmed/31040369 http://dx.doi.org/10.1038/s41598-019-43261-z |
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