A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/105848 https://doi.org/10.3390/cancers12020495 |
Resumo: | 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. |
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A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensincancer stem cellsgastric cancerSOX2monensinSORE6-GFP reporter systemdrug resistancehigh-throughput screeningGastric 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.MDPI2020-02-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105848http://hdl.handle.net/10316/105848https://doi.org/10.3390/cancers12020495eng2072-6694Pádua, DianaBarros, RitaAmaral, Ana LuísaMesquita, PatríciaFreire, Ana FilipaSousa, MafaldaMaia, André FilipeCaiado, InêsFernandes, HugoPombinho, AntónioPereira, Carlos FilipeAlmeida, Raquelinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T21:34:24Zoai:estudogeral.uc.pt:10316/105848Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:20.787045Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin Pádua, Diana cancer stem cells gastric cancer SOX2 monensin SORE6-GFP reporter system drug resistance high-throughput screening |
title_short |
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_sort |
A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin |
author |
Pádua, Diana |
author_facet |
Pádua, Diana Barros, Rita Amaral, Ana Luísa Mesquita, Patrícia Freire, Ana Filipa Sousa, Mafalda Maia, André Filipe Caiado, Inês Fernandes, Hugo Pombinho, António Pereira, Carlos Filipe Almeida, Raquel |
author_role |
author |
author2 |
Barros, Rita Amaral, Ana Luísa Mesquita, Patrícia Freire, Ana Filipa Sousa, Mafalda Maia, André Filipe Caiado, Inês Fernandes, Hugo Pombinho, António Pereira, Carlos Filipe Almeida, Raquel |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Pádua, Diana Barros, Rita Amaral, Ana Luísa Mesquita, Patrícia Freire, Ana Filipa Sousa, Mafalda Maia, André Filipe Caiado, Inês Fernandes, Hugo Pombinho, António Pereira, Carlos Filipe Almeida, Raquel |
dc.subject.por.fl_str_mv |
cancer stem cells gastric cancer SOX2 monensin SORE6-GFP reporter system drug resistance high-throughput screening |
topic |
cancer stem cells gastric cancer SOX2 monensin SORE6-GFP reporter system drug resistance high-throughput screening |
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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-02-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/105848 http://hdl.handle.net/10316/105848 https://doi.org/10.3390/cancers12020495 |
url |
http://hdl.handle.net/10316/105848 https://doi.org/10.3390/cancers12020495 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2072-6694 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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