{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:54:16Z","timestamp":1771026856534,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T00:00:00Z","timestamp":1693699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Norte Portugal Regional Operational Programme (NORTE 2020)","award":["Norte-01-0145-FEDER-000051"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000051"]}]},{"name":"Norte Portugal Regional Operational Programme (NORTE 2020)","award":["SFRH\/BD\/146186\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146186\/2019"]}]},{"name":"Norte Portugal Regional Operational Programme (NORTE 2020)","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["Norte-01-0145-FEDER-000051"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000051"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["SFRH\/BD\/146186\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146186\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"Programa Operacional Regional do Norte and European Regional Development Fund under the project \u201cThe Porto Comprehensive Cancer Center\u201d","award":["Norte-01-0145-FEDER-000051"],"award-info":[{"award-number":["Norte-01-0145-FEDER-000051"]}]},{"name":"Programa Operacional Regional do Norte and European Regional Development Fund under the project \u201cThe Porto Comprehensive Cancer Center\u201d","award":["SFRH\/BD\/146186\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146186\/2019"]}]},{"name":"Programa Operacional Regional do Norte and European Regional Development Fund under the project \u201cThe Porto Comprehensive Cancer Center\u201d","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6\u2212), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6\u2212 to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1\u03b1, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.<\/jats:p>","DOI":"10.3390\/cancers15174406","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:43:20Z","timestamp":1693795400000},"page":"4406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9842","authenticated-orcid":false,"given":"Diana","family":"P\u00e1dua","sequence":"first","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"ICBAS\u2014Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Paula","family":"Figueira","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Mariana","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-7016","authenticated-orcid":false,"given":"Andr\u00e9 Filipe","family":"Maia","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Institute of Molecular and Cell Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-5680","authenticated-orcid":false,"given":"Joana","family":"Peixoto","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-9659","authenticated-orcid":false,"given":"Raquel T.","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"Pathology Department, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Pombinho","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Institute of Molecular and Cell Biology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-1382","authenticated-orcid":false,"given":"Carlos Filipe","family":"Pereira","sequence":"additional","affiliation":[{"name":"CNC\u2014Center 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\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"Pathology Department, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-9831","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Mesquita","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer 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