Cancers, Vol. 12, Pages 495: A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

Cancers, Vol. 12, Pages 495: A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin Cancers doi: 10.3390/cancers12020495 Authors: Pádua Barros Amaral Mesquita Freire Sousa Maia Caiado Fernandes Pombinho Pereira Almeida 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-GF...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research