2026-04-29T15:25:29Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/96892025-04-29T10:06:24Zcom_20.500.12105_14556com_20.500.12105_2337com_20.500.12105_2336com_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_14558col_20.500.12105_19616col_20.500.12105_16990
Repisalud
author
Menéndez, Sofía T
author
Rey, Veronica
author
Martinez-Cruzado, Lucia
author
González, M Victoria
author
Morales-Molina, Alvaro
author
Santos, Laura
author
Blanco, Verónica
author
Alvarez, Carlos
author
Estupiñan, Oscar
author
Allonca, Eva
author
Rodrigo, Juan Pablo
author
Garcia-Castro, Javier
author
Garcia-Pedrero, Juana Maria
author
Rodriguez, Rene
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Gobierno del Principado de Asturias (España)
2020-04-22T17:01:05Z
2020-04-22T17:01:05Z
2020-04-13
Cancers (Basel). 2020 Apr 13;12(4). pii: E964.
10.3390/cancers12040964
2072-6694
Cancers
32295077
http://hdl.handle.net/20.500.12105/9689
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.
eng
EC-8042
SOX2
Cancer stem cells
Chondrosarcoma
Sarcoma
Undifferentiated pleomorphic sarcoma
SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications
research article
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URL
https://repisalud.isciii.es/bitstreams/f98ce288-5942-4933-a481-c062c74a5064/download
File
MD5
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application/pdf
SOX2ExpressionandTranscriptional_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/46d75694-e286-4ad3-99ba-dbe82755f59d/download
File
MD5
3e308e7312672b6d59a9deea3ba42eea
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text/plain
SOX2ExpressionandTranscriptional_2020.pdf.txt