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00925njm 22002777a 4500 dc 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 author 2020-04-13 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. Cancers (Basel). 2020 Apr 13;12(4). pii: E964. 10.3390/cancers12040964 2072-6694 Cancers 32295077 http://hdl.handle.net/20.500.12105/9689 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