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Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer
Epithelial–mesenchymal transition (EMT) and its reverse process, mesenchymal–epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial–mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processe...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480077/ https://www.ncbi.nlm.nih.gov/pubmed/28371195 http://dx.doi.org/10.1111/cas.13246 |
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author | Yamamoto, Mizuki Sakane, Kota Tominaga, Kana Gotoh, Noriko Niwa, Takayoshi Kikuchi, Yasuko Tada, Keiichiro Goshima, Naoki Semba, Kentaro Inoue, Jun‐ichiro |
author_facet | Yamamoto, Mizuki Sakane, Kota Tominaga, Kana Gotoh, Noriko Niwa, Takayoshi Kikuchi, Yasuko Tada, Keiichiro Goshima, Naoki Semba, Kentaro Inoue, Jun‐ichiro |
author_sort | Yamamoto, Mizuki |
collection | PubMed |
description | Epithelial–mesenchymal transition (EMT) and its reverse process, mesenchymal–epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial–mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re‐undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple‐negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus‐labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E‐box‐binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT–MET dynamics that could affect the development of triple‐negative breast cancer. |
format | Online Article Text |
id | pubmed-5480077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54800772017-06-23 Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer Yamamoto, Mizuki Sakane, Kota Tominaga, Kana Gotoh, Noriko Niwa, Takayoshi Kikuchi, Yasuko Tada, Keiichiro Goshima, Naoki Semba, Kentaro Inoue, Jun‐ichiro Cancer Sci Original Articles Epithelial–mesenchymal transition (EMT) and its reverse process, mesenchymal–epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial–mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re‐undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple‐negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus‐labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E‐box‐binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT–MET dynamics that could affect the development of triple‐negative breast cancer. John Wiley and Sons Inc. 2017-05-21 2017-06 /pmc/articles/PMC5480077/ /pubmed/28371195 http://dx.doi.org/10.1111/cas.13246 Text en © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Yamamoto, Mizuki Sakane, Kota Tominaga, Kana Gotoh, Noriko Niwa, Takayoshi Kikuchi, Yasuko Tada, Keiichiro Goshima, Naoki Semba, Kentaro Inoue, Jun‐ichiro Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title | Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title_full | Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title_fullStr | Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title_full_unstemmed | Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title_short | Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
title_sort | intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480077/ https://www.ncbi.nlm.nih.gov/pubmed/28371195 http://dx.doi.org/10.1111/cas.13246 |
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