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A SOX2 reporter sys...
A SOX2 reporter system identifies gastric cancer stem-like cells sensitive to monensin
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- Pádua, Diana (author)
- University of Porto
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- Barros, Rita (author)
- University of Porto
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- Amaral, Ana Luísa (author)
- University of Porto
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- Mesquita, Patrícia (author)
- University of Porto
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- Freire, Ana Filipa (author)
- University of Porto
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- Sousa, Mafalda (author)
- Institute for Molecular and Cell Biology
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- Maia, André Filipe (author)
- Institute for Molecular and Cell Biology
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- Caiado, Inês (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cellulär omprogrammering i hematopoes och immunitet,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Cell Reprogramming in Hematopoiesis and Immunity,Lund University Research Groups,University of Coimbra
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- Fernandes, Hugo (author)
- University of Coimbra
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- Pombinho, António (author)
- Institute for Molecular and Cell Biology
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- Pereira, Carlos Filipe (author)
- Lund University,Lunds universitet,Cellulär omprogrammering i hematopoes och immunitet,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cell Reprogramming in Hematopoiesis and Immunity,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,University of Coimbra
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- Almeida, Raquel (author)
- University of Porto
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(creator_code:org_t)
- 2020-02-20
- 2020
- English.
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:2
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https://doi.org/10.3...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Keyword
- Cancer stem cells
- Drug resistance
- Gastric cancer
- Monensin
- Shigh-throughput screening
- SORE6-GFP reporter system
- SOX2
Publication and Content Type
- art (subject category)
- ref (subject category)
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Cancers
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- By the author/editor
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Pádua, Diana
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Barros, Rita
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Amaral, Ana Luís ...
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Mesquita, Patríc ...
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Freire, Ana Fili ...
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Sousa, Mafalda
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Maia, André Fili ...
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Caiado, Inês
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Fernandes, Hugo
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Pombinho, Antóni ...
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Pereira, Carlos ...
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Almeida, Raquel
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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Cancers
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Lund University