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

Diana Pádua, Rita Barros, Ana Luísa Amaral, Patrícia Mesquita, Ana Filipa Freire, Mafalda Sousa, André Filipe Maia, Inês Caiado, Hugo Fernandes, António Pombinho, Carlos Filipe Pereira, Raquel Almeida

Research output: Contribution to journalArticlepeer-review

10 Citations (SciVal)

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.

Original languageEnglish
Article number495
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - 2020

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Medical Biotechnology

Keywords

  • Cancer stem cells
  • Drug resistance
  • Gastric cancer
  • Monensin
  • Shigh-throughput screening
  • SORE6-GFP reporter system
  • SOX2

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