The Experts below are selected from a list of 12510 Experts worldwide ranked by ideXlab platform

Stefanie Stein - One of the best experts on this subject based on the ideXlab platform.

  • oncogenic hijacking of a developmental Transcription Factor evokes vulnerability toward oxidative stress in ewing sarcoma
    Nature Communications, 2020
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, David Saucier, Chiara Arrigoni, Maria V Colombo, Victor Bardinet, Stefanie Stein
    Abstract:

    Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high Sox6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

  • oncogenic hijacking of a developmental Transcription Factor evokes therapeutic vulnerability for ros induction in ewing sarcoma
    bioRxiv, 2019
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, Stefanie Stein, David Saucier, Chiara Arrigoni, Julia S Gerke, Michaela C Baldauf
    Abstract:

    ABSTRACT Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that Sox6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

Aruna Marchetto - One of the best experts on this subject based on the ideXlab platform.

  • oncogenic hijacking of a developmental Transcription Factor evokes vulnerability toward oxidative stress in ewing sarcoma
    Nature Communications, 2020
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, David Saucier, Chiara Arrigoni, Maria V Colombo, Victor Bardinet, Stefanie Stein
    Abstract:

    Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high Sox6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

  • oncogenic hijacking of a developmental Transcription Factor evokes therapeutic vulnerability for ros induction in ewing sarcoma
    bioRxiv, 2019
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, Stefanie Stein, David Saucier, Chiara Arrigoni, Julia S Gerke, Michaela C Baldauf
    Abstract:

    ABSTRACT Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that Sox6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

David Saucier - One of the best experts on this subject based on the ideXlab platform.

  • oncogenic hijacking of a developmental Transcription Factor evokes vulnerability toward oxidative stress in ewing sarcoma
    Nature Communications, 2020
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, David Saucier, Chiara Arrigoni, Maria V Colombo, Victor Bardinet, Stefanie Stein
    Abstract:

    Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high Sox6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

  • oncogenic hijacking of a developmental Transcription Factor evokes therapeutic vulnerability for ros induction in ewing sarcoma
    bioRxiv, 2019
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, Stefanie Stein, David Saucier, Chiara Arrigoni, Julia S Gerke, Michaela C Baldauf
    Abstract:

    ABSTRACT Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that Sox6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

Maximilian M L Knott - One of the best experts on this subject based on the ideXlab platform.

  • oncogenic hijacking of a developmental Transcription Factor evokes vulnerability toward oxidative stress in ewing sarcoma
    Nature Communications, 2020
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, David Saucier, Chiara Arrigoni, Maria V Colombo, Victor Bardinet, Stefanie Stein
    Abstract:

    Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high Sox6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

  • oncogenic hijacking of a developmental Transcription Factor evokes therapeutic vulnerability for ros induction in ewing sarcoma
    bioRxiv, 2019
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, Stefanie Stein, David Saucier, Chiara Arrigoni, Julia S Gerke, Michaela C Baldauf
    Abstract:

    ABSTRACT Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that Sox6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

Shunya Ohmura - One of the best experts on this subject based on the ideXlab platform.

  • oncogenic hijacking of a developmental Transcription Factor evokes vulnerability toward oxidative stress in ewing sarcoma
    Nature Communications, 2020
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, David Saucier, Chiara Arrigoni, Maria V Colombo, Victor Bardinet, Stefanie Stein
    Abstract:

    Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 - a physiological driver of proliferation of osteo-chondrogenic progenitors - by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high Sox6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.

  • oncogenic hijacking of a developmental Transcription Factor evokes therapeutic vulnerability for ros induction in ewing sarcoma
    bioRxiv, 2019
    Co-Authors: Aruna Marchetto, Shunya Ohmura, Martin F Orth, Fabienne S Wehweck, Maximilian M L Knott, Stefanie Stein, David Saucier, Chiara Arrigoni, Julia S Gerke, Michaela C Baldauf
    Abstract:

    ABSTRACT Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of Transcription Factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites (mSats) as enhancers. Here, we show that EWSR1-FLI1 hijacks the developmental Transcription Factor Sox6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-mSat, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments, we discovered that Sox6 interferes with the antioxidant system resulting in constitutively elevated reactive oxygen species (ROS) levels that create a therapeutic vulnerability toward the ROS-inducing drug Elesclomol. Collectively, our results exemplify how aberrant activation of a developmental Transcription Factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.