Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors

Zayed, Heba; Petersen, Iver

doi:10.1016/j.prp.2018.05.004

Cited by 14 publications

(11 citation statements)

References 161 publications

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“…We found that SOX2 is expressed in 28% of an array of 88 sarcoma patients, being UPS, synovial sarcomas and Ewing sarcomas those presenting a higher percentage of positive cases in concordance with the results of previous reports [43,44]. In our series, SOX2 expression significantly correlated with tumor grade, poor differentiation, invasive potential and poor patient survival.…”

Section: Discussionsupporting

confidence: 91%

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications

Menéndez

Rey

Martinez-Cruzado

et al. 2020

Cancers

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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.

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Section: Discussionsupporting

confidence: 91%

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications

Menéndez

Rey

Martinez-Cruzado

et al. 2020

Cancers

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“…Finally, ATP-dependent chromatin remodelers, such as SWI/SNF, ISWI, and CHD, are implicated in tumor initiation, sarcomagenesis and maintenance of a stem-like phenotype in STS [17], namely in myxoid liposarcoma [74], SS [75], or RMS [76]. Table 1 summarizes the CSC markers that have been used to identify, isolate and characterize CSCs in different STS subtypes.…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

“…Myxoid Liposarcoma SWI/ SNF, ISWI and CHD [74] In vitro MPNST 1 Nestin [36] In vitro and in vivo Rhabdomyosarcoma ALDH [39] In vitro and in vivo CD133 [19][20][21] In vitro, in vivo and patient samples DNMT3B [68] In vitro EZH2 [69] In vitro and in vivo Nestin [19,27,[33][34][35] In vitro, in vivo and patient samples NOTCH-YAP1-Sox2 [62] In vitro, in vivo and patient samples Side Population [54] In vitro, in vivo and patient samples Embryonic stem cell transcription factors [64] In vitro, in vivo and patient samples SWI/ SNF, ISWI and CHD [76] In vitro, in vivo and patient samples Synovial Sarcoma ALDH [40] In vitro Active Wnt pathway [77] In vitro and in vivo BMI1 [23] In vitro CD133 [23,25] In vitro and patient samples CXCR4 [28] In vitro, in vivo and patient samples EZH2 [70][71][72] In vitro, in vivo and patient samples SWI/ SNF, ISWI and CHD [75] Patient samples UPS 2 Side Population [54] In vitro, in vivo and patient samples ABC transporters [51] In vitro CD133 [51] In vitro Embryonic stem cell transcription factors [51] In vitro 1 MPNST: Malignant peripheral nerve sheath tumor; 2 UPS: Undifferentiated pleomorphic sarcoma.…”

Section: Sts Subtype Csc Marker/feature Evidencementioning

confidence: 99%

Cancer Stem Cells in Soft-Tissue Sarcomas

Martínez-Delgado

Lacerenza

Obrador‐Hevia

et al. 2020

Cells

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Soft tissue sarcomas (STS) are a rare group of mesenchymal solid tumors with heterogeneous genetic profiles and clinical features. Systemic chemotherapy is the backbone treatment for advanced STS; however, STS frequently acquire resistance to standard therapies, which highlights the need to improve treatments and identify novel therapeutic targets. Increases in the knowledge of the molecular pathways that drive sarcomas have brought to light different molecular alterations that cause tumor initiation and progression. These findings have triggered a breakthrough of targeted therapies that are being assessed in clinical trials. Cancer stem cells (CSCs) exhibit mesenchymal stem cell (MSC) features and represent a subpopulation of tumor cells that play an important role in tumor progression, chemotherapy resistance, recurrence and metastasis. In fact, CSCs phenotypes have been identified in sarcomas, allied to drug resistance and tumorigenesis. Herein, we will review the published evidence of CSCs in STS, discussing the molecular characteristic of CSCs, the commonly used isolation techniques and the new possibilities of targeting CSCs as a way to improve STS treatment and consequently patient outcome.

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“…In addition to their essential functions during embryonic development, these genes could exert diverse functions in cancer. In certain human tumors, they might represent valuable tools to predict recurrence and tumor plasticity, although such prognostic value is far from being established [ 79 , 89 , 90 , 91 , 92 , 93 , 94 ].…”

Section: Mechanisms Of Hypoxia-induced Cancer Stem Cellsmentioning

confidence: 99%

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

Terry

Zaarour

Venkatesh

et al. 2018

IJMS

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Hypoxia, or gradients of hypoxia, occurs in most growing solid tumors and may result in pleotropic effects contributing significantly to tumor aggressiveness and therapy resistance. Indeed, the generated hypoxic stress has a strong impact on tumor cell biology. For example, it may contribute to increasing tumor heterogeneity, help cells gain new functional properties and/or select certain cell subpopulations, facilitating the emergence of therapeutic resistant cancer clones, including cancer stem cells coincident with tumor relapse and progression. It controls tumor immunogenicity, immune plasticity, and promotes the differentiation and expansion of immune-suppressive stromal cells. In this context, manipulation of the hypoxic microenvironment may be considered for preventing or reverting the malignant transformation. Here, we review the current knowledge on how hypoxic stress in tumor microenvironments impacts on tumor heterogeneity, plasticity and resistance, with a special interest in the impact on immune resistance and tumor immunogenicity.

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Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors

Cited by 14 publications

References 161 publications

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications

SOX2 Expression and Transcriptional Activity Identifies a Subpopulation of Cancer Stem Cells in Sarcoma with Prognostic Implications

Cancer Stem Cells in Soft-Tissue Sarcomas

Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity

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