{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:45:44Z","timestamp":1790790344520,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["SAF-2016-75286-R"],"award-info":[{"award-number":["SAF-2016-75286-R"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CPII16\/00049"],"award-info":[{"award-number":["CPII16\/00049"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD16\/00103"],"award-info":[{"award-number":["CD16\/00103"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/00280"],"award-info":[{"award-number":["PI16\/00280"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00560"],"award-info":[{"award-number":["PI19\/00560"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/12\/00390"],"award-info":[{"award-number":["CB16\/12\/00390"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011941","name":"Gobierno del Principado de Asturias","doi-asserted-by":"publisher","award":["IDI\/2018\/155"],"award-info":[{"award-number":["IDI\/2018\/155"]}],"id":[{"id":"10.13039\/100011941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011941","name":"Gobierno del Principado de Asturias","doi-asserted-by":"publisher","award":["BP-17-108"],"award-info":[{"award-number":["BP-17-108"]}],"id":[{"id":"10.13039\/100011941","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Stemness in sarcomas is coordinated by the expression of pluripotency factors, like SOX2, in cancer stem cells (CSC). The role of SOX2 in tumor initiation and progression has been well characterized in osteosarcoma. However, the pro-tumorigenic features of SOX2 have been scarcely investigated in other sarcoma subtypes. Here, we show that SOX2 depletion dramatically reduced the ability of undifferentiated pleomorphic sarcoma (UPS) cells to form tumorspheres and to initiate tumor growth. Conversely, SOX2 overexpression resulted in increased in vivo tumorigenicity. Moreover, using a reporter system (SORE6) which allows to monitor viable cells expressing SOX2 and\/or OCT4, we found that SORE6+ cells were significantly more tumorigenic than the SORE6- subpopulation. In agreement with this findings, SOX2 expression in sarcoma patients was associated to tumor grade, differentiation, invasive potential and lower patient survival. Finally, we studied the effect of a panel of anti-tumor drugs on the SORE6+ cells of the UPS model and patient-derived chondrosarcoma lines. We found that the mithramycin analogue EC-8042 was the most efficient in reducing SORE6+ cells in vitro and in vivo. Overall, this study demonstrates that SOX2 is a pro-tumorigenic factor with prognostic potential in sarcoma. Moreover, SORE6 transcriptional activity is a bona fide CSC marker in sarcoma and constitutes an excellent biomarker for evaluating the efficacy of anti-tumor treatments on CSC subpopulations.<\/jats:p>","DOI":"10.3390\/cancers12040964","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T03:10:01Z","timestamp":1586833801000},"page":"964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications"],"prefix":"10.3390","volume":"12","author":[{"given":"Sofia T.","family":"Menendez","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"},{"name":"CIBER en oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Rey","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Martinez-Cruzado","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Victoria","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"},{"name":"CIBER en oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"},{"name":"Departamento de Cirug\u00eda, Universidad de Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4532-7667","authenticated-orcid":false,"given":"Alvaro","family":"Morales-Molina","sequence":"additional","affiliation":[{"name":"Cellular Biotechnology Unit, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Santos","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Estupi\u00f1an","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"},{"name":"CIBER en oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-5421","authenticated-orcid":false,"given":"Eva","family":"Allonca","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)\u2014Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33006 Oviedo, Spain"},{"name":"CIBER en oncolog\u00eda (CIBERONC), 28029 Madrid, 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Oviedo, Spain"},{"name":"CIBER en oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.stem.2012.05.007","article-title":"Cancer stem cells: Current status and evolving complexities","volume":"10","author":"Visvader","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1128\/MCB.25.14.6031-6046.2005","article-title":"Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4\/Sox2 complex in embryonic stem cells","volume":"25","author":"Chew","year":"2005","journal-title":"Mol. 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