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Myosin II Reactivation and Cytoskeletal Remodeling as a Hallmark and a Vulnerability in Melanoma Therapy Resistance.
Orgaz, Jose L; Crosas-Molist, Eva; Sadok, Amine; Perdrix-Rosell, Anna; Maiques, Oscar; Rodriguez-Hernandez, Irene; Monger, Jo; Mele, Silvia; Georgouli, Mirella; Bridgeman, Victoria; Karagiannis, Panagiotis; Lee, Rebecca; Pandya, Pahini; Boehme, Lena; Wallberg, Fredrik; Tape, Chris; Karagiannis, Sophia N; Malanchi, Ilaria; Sanz-Moreno, Victoria.
Afiliación
  • Orgaz JL; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK. Electronic address: j.orgaz@qmul.ac.uk.
  • Crosas-Molist E; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Sadok A; Translational Cancer Discovery Team, Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, UK.
  • Perdrix-Rosell A; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK; Tumour Host Interaction, The Francis Crick Inst
  • Maiques O; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Rodriguez-Hernandez I; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Monger J; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK.
  • Mele S; St. John's Institute of Dermatology, King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, London SE1 9RT, UK.
  • Georgouli M; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Bridgeman V; Tumour Host Interaction, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Karagiannis P; St. John's Institute of Dermatology, King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, London SE1 9RT, UK; Department of Oncology, Haematology and Stem Cell Transplantation, University Hospital of Hamburg Eppendorf, Hamburg 202
  • Lee R; Molecular Oncology Group, Cancer Research UK Manchester Institute, Manchester M20 4BX, UK.
  • Pandya P; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Boehme L; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
  • Wallberg F; The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
  • Tape C; Cell Communication Lab, UCL Cancer Institute, 72 Huntley Street, London WC1E 6DD, UK.
  • Karagiannis SN; St. John's Institute of Dermatology, King's College London & NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals and King's College London, London SE1 9RT, UK.
  • Malanchi I; Tumour Host Interaction, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Sanz-Moreno V; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, UK; Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK. Electronic address: v.sanz-moreno@qmul.ac.uk.
Cancer Cell ; 37(1): 85-103.e9, 2020 01 13.
Article en En | MEDLINE | ID: mdl-31935375
ABSTRACT
Despite substantial clinical benefit of targeted and immune checkpoint blockade-based therapies in melanoma, resistance inevitably develops. We show cytoskeletal remodeling and changes in expression and activity of ROCK-myosin II pathway during acquisition of resistance to MAPK inhibitors. MAPK regulates myosin II activity, but after initial therapy response, drug-resistant clones restore myosin II activity to increase survival. High ROCK-myosin II activity correlates with aggressiveness, identifying targeted therapy- and immunotherapy-resistant melanomas. Survival of resistant cells is myosin II dependent, regardless of the therapy. ROCK-myosin II ablation specifically kills resistant cells via intrinsic lethal reactive oxygen species and unresolved DNA damage and limits extrinsic myeloid and lymphoid immunosuppression. Efficacy of targeted therapies and immunotherapies can be improved by combination with ROCK inhibitors.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Citoesqueleto / Resistencia a Antineoplásicos / Miosina Tipo II / Melanoma Límite: Animals / Female / Humans / Male Idioma: En Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Citoesqueleto / Resistencia a Antineoplásicos / Miosina Tipo II / Melanoma Límite: Animals / Female / Humans / Male Idioma: En Año: 2020 Tipo del documento: Article