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A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin
Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to is...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072720/ https://www.ncbi.nlm.nih.gov/pubmed/32093282 http://dx.doi.org/10.3390/cancers12020495 |
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author | Pádua, Diana Barros, Rita Luísa Amaral, Ana Mesquita, Patrícia Filipa Freire, Ana Sousa, Mafalda Filipe Maia, André Caiado, Inês Fernandes, Hugo Pombinho, António Filipe Pereira, Carlos Almeida, Raquel |
author_facet | Pádua, Diana Barros, Rita Luísa Amaral, Ana Mesquita, Patrícia Filipa Freire, Ana Sousa, Mafalda Filipe Maia, André Caiado, Inês Fernandes, Hugo Pombinho, António Filipe Pereira, Carlos Almeida, Raquel |
author_sort | Pádua, Diana |
collection | PubMed |
description | Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6– cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs. |
format | Online Article Text |
id | pubmed-7072720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70727202020-03-19 A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin Pádua, Diana Barros, Rita Luísa Amaral, Ana Mesquita, Patrícia Filipa Freire, Ana Sousa, Mafalda Filipe Maia, André Caiado, Inês Fernandes, Hugo Pombinho, António Filipe Pereira, Carlos Almeida, Raquel Cancers (Basel) Article Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6– cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs. MDPI 2020-02-20 /pmc/articles/PMC7072720/ /pubmed/32093282 http://dx.doi.org/10.3390/cancers12020495 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pádua, Diana Barros, Rita Luísa Amaral, Ana Mesquita, Patrícia Filipa Freire, Ana Sousa, Mafalda Filipe Maia, André Caiado, Inês Fernandes, Hugo Pombinho, António Filipe Pereira, Carlos Almeida, Raquel A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title_full | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title_fullStr | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title_full_unstemmed | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title_short | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
title_sort | sox2 reporter system identifies gastric cancer stem-like cells sensitive to monensin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072720/ https://www.ncbi.nlm.nih.gov/pubmed/32093282 http://dx.doi.org/10.3390/cancers12020495 |
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