{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T16:55:26Z","timestamp":1769014526075,"version":"3.49.0"},"reference-count":81,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["POCI-01-0145-FEDER-016390"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["POCI-01-0145-FEDER-029017"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["SFRH\/BD\/146186\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146186\/2019"]}]},{"name":"COMPETE 2020 \u2013 Operacional Programme for Competitiveness and Internationalisation","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"COMPETE 2020 \u2013 Operacional Programme for Competitiveness and Internationalisation","award":["NORTE-07-0124-FEDER-000029"],"award-info":[{"award-number":["NORTE-07-0124-FEDER-000029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats: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\u2013 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.<\/jats:p>","DOI":"10.3390\/cancers12020495","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T04:21:26Z","timestamp":1582604486000},"page":"495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9842","authenticated-orcid":false,"given":"Diana","family":"P\u00e1dua","sequence":"first","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Rita","family":"Barros","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Ana Lu\u00edsa","family":"Amaral","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Patr\u00edcia","family":"Mesquita","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Ana Filipa","family":"Freire","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Mafalda","family":"Sousa","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Institute of Molecular and Cell Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Andr\u00e9 Filipe","family":"Maia","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Institute of Molecular and Cell Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"In\u00eas","family":"Caiado","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Cell Reprogramming in Hematopoiesis and Immunity laboratory, Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden"},{"name":"Wallenberg Center for Molecular Medicine, Lund University, 221 84 Lund, Sweden"}]},{"given":"Hugo","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal"}]},{"given":"Ant\u00f3nio","family":"Pombinho","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC-Institute of Molecular and Cell Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Carlos Filipe","family":"Pereira","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Cell Reprogramming in Hematopoiesis and Immunity laboratory, Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden"},{"name":"Wallenberg Center for Molecular Medicine, Lund University, 221 84 Lund, Sweden"}]},{"given":"Raquel","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S-Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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