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A SOX2 reporter system identifies gastric cancer stem-like cells sensitive to monensin

Pádua, Diana ; Barros, Rita ; Amaral, Ana Luísa ; Mesquita, Patrícia ; Freire, Ana Filipa ; Sousa, Mafalda ; Maia, André Filipe ; Caiado, Inês LU ; Fernandes, Hugo and Pombinho, António , et al. (2020) In Cancers 12(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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer stem cells, Drug resistance, Gastric cancer, Monensin, Shigh-throughput screening, SORE6-GFP reporter system, SOX2
in
Cancers
volume
12
issue
2
article number
495
publisher
MDPI AG
external identifiers
  • scopus:85079728151
  • pmid:32093282
ISSN
2072-6694
DOI
10.3390/cancers12020495
language
English
LU publication?
yes
id
c5f5ab16-44d8-478a-8666-b862ddbb7f99
date added to LUP
2020-03-10 15:33:47
date last changed
2024-06-26 11:38:55
@article{c5f5ab16-44d8-478a-8666-b862ddbb7f99,
  abstract     = {{<p>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.</p>}},
  author       = {{Pádua, Diana and Barros, Rita and Amaral, Ana Luísa and Mesquita, Patrícia and Freire, Ana Filipa and Sousa, Mafalda and Maia, André Filipe and Caiado, Inês and Fernandes, Hugo and Pombinho, António and Pereira, Carlos Filipe and Almeida, Raquel}},
  issn         = {{2072-6694}},
  keywords     = {{Cancer stem cells; Drug resistance; Gastric cancer; Monensin; Shigh-throughput screening; SORE6-GFP reporter system; SOX2}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{A SOX2 reporter system identifies gastric cancer stem-like cells sensitive to monensin}},
  url          = {{http://dx.doi.org/10.3390/cancers12020495}},
  doi          = {{10.3390/cancers12020495}},
  volume       = {{12}},
  year         = {{2020}},
}