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Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma.
Yu, Yong; Schleich, Kolja; Yue, Bin; Ji, Sujuan; Lohneis, Philipp; Kemper, Kristel; Silvis, Mark R; Qutob, Nouar; van Rooijen, Ellen; Werner-Klein, Melanie; Li, Lianjie; Dhawan, Dhriti; Meierjohann, Svenja; Reimann, Maurice; Elkahloun, Abdel; Treitschke, Steffi; Dörken, Bernd; Speck, Christian; Mallette, Frédérick A; Zon, Leonard I; Holmen, Sheri L; Peeper, Daniel S; Samuels, Yardena; Schmitt, Clemens A; Lee, Soyoung.
Afiliação
  • Yu Y; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany.
  • Schleich K; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Yue B; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Ji S; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Lohneis P; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, 10117 Berlin, Germany.
  • Kemper K; Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
  • Silvis MR; Department of Surgery, University of Utah Health Sciences Center & Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
  • Qutob N; Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot 7610001, Israel.
  • van Rooijen E; Howard Hughes Medical Institute, Stem Cell Program and the Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge,
  • Werner-Klein M; Regensburg Center for Interventional Immunology (RCI) and University Medical Center of Regensburg, 93053 Regensburg, Germany; Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany.
  • Li L; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Dhawan D; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Meierjohann S; University of Würzburg, Physiological Chemistry, Biocenter, 97074 Würzburg, Germany.
  • Reimann M; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molekulares Krebsforschungszentrum, 13353 Berlin, Germany.
  • Elkahloun A; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Treitschke S; Fraunhofer-Institute for Toxicology and Experimental Medicine, 93053 Regensburg, Germany.
  • Dörken B; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Imm
  • Speck C; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, and MRC London Institute of Medical Sciences (LMS), London W12 0NN, UK.
  • Mallette FA; Department of Medicine, Université de Montréal, Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC H1T 2M4, Canada.
  • Zon LI; Howard Hughes Medical Institute, Stem Cell Program and the Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge,
  • Holmen SL; Department of Surgery, University of Utah Health Sciences Center & Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
  • Peeper DS; Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
  • Samuels Y; Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot 7610001, Israel.
  • Schmitt CA; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Imm
  • Lee S; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department of Hematology, Oncology and Tumor Imm
Cancer Cell ; 33(2): 322-336.e8, 2018 02 12.
Article em En | MEDLINE | ID: mdl-29438700
ABSTRACT
Oncogene-induced senescence, e.g., in melanocytic nevi, terminates the expansion of pre-malignant cells via transcriptional silencing of proliferation-related genes due to decoration of their promoters with repressive trimethylated histone H3 lysine 9 (H3K9) marks. We show here that structurally distinct H3K9-active demethylases-the lysine-specific demethylase-1 (LSD1) and several Jumonji C domain-containing moieties (such as JMJD2C)-disable senescence and permit Ras/Braf-evoked transformation. In mouse and zebrafish models, enforced LSD1 or JMJD2C expression promoted Braf-V600E-driven melanomagenesis. A large subset of established melanoma cell lines and primary human melanoma samples presented with a collective upregulation of related and unrelated H3K9 demethylase activities, whose targeted inhibition restored senescence, even in Braf inhibitor-resistant melanomas, evoked secondary immune effects and controlled tumor growth in vivo.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histona Desmetilases / Histona Desmetilases com o Domínio Jumonji / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histona Desmetilases / Histona Desmetilases com o Domínio Jumonji / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha