Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/105848
Title: | A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin | Authors: | 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 |
Keywords: | cancer stem cells; gastric cancer; SOX2; monensin; SORE6-GFP reporter system; drug resistance; high-throughput screening | Issue Date: | 20-Feb-2020 | Publisher: | MDPI | Project: | project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) project NORTE-07-0124-FEDER-000029 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) POCI-01-0145-FEDER-029017 POCI-01-0145-FEDER-016390 PhD fellowship (SFRH/BD/146186/2019) |
Serial title, monograph or event: | Cancers | Volume: | 12 | Issue: | 2 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/105848 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers12020495 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
A-SOX2-reporter-system-identifies-gastric-cancer-stemlike-cells-sensitive-to-monensinCancers.pdf | 3.76 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
33
checked on Aug 12, 2024
WEB OF SCIENCETM
Citations
31
checked on Aug 2, 2024
Page view(s)
95
checked on Aug 13, 2024
Download(s)
36
checked on Aug 13, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License