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Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics.
Lalaoui, Najoua; Hänggi, Kay; Brumatti, Gabriela; Chau, Diep; Nguyen, Nhu-Y N; Vasilikos, Lazaros; Spilgies, Lisanne M; Heckmann, Denise A; Ma, Chunyan; Ghisi, Margherita; Salmon, Jessica M; Matthews, Geoffrey M; de Valle, Elisha; Moujalled, Donia M; Menon, Manoj B; Spall, Sukhdeep Kaur; Glaser, Stefan P; Richmond, Jennifer; Lock, Richard B; Condon, Stephen M; Gugasyan, Raffi; Gaestel, Matthias; Guthridge, Mark; Johnstone, Ricky W; Munoz, Lenka; Wei, Andrew; Ekert, Paul G; Vaux, David L; Wong, W Wei-Lynn; Silke, John.
Afiliación
  • Lalaoui N; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Hänggi K; Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
  • Brumatti G; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Chau D; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Nguyen NY; Department of Clinical Hematology, The Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
  • Vasilikos L; Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
  • Spilgies LM; Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
  • Heckmann DA; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Ma C; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Ghisi M; Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Salmon JM; Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Matthews GM; Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3050, Australia.
  • de Valle E; Immunomonitoring Facility and Centre for Biomedical Research, The Burnet Institute, Melbourne, VIC 3004, Australia; Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC 3181, Australia.
  • Moujalled DM; Department of Clinical Hematology, The Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
  • Menon MB; Institute of Physiological Chemistry, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany.
  • Spall SK; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Glaser SP; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Richmond J; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW 2031, Australia.
  • Lock RB; Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW 2031, Australia.
  • Condon SM; TetraLogic Pharmaceuticals Corporation, 343 Phoenixville Pike, Malvern, PA 19355, USA.
  • Gugasyan R; Immunomonitoring Facility and Centre for Biomedical Research, The Burnet Institute, Melbourne, VIC 3004, Australia; Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC 3181, Australia.
  • Gaestel M; Institute of Physiological Chemistry, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany.
  • Guthridge M; Department of Clinical Hematology, The Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
  • Johnstone RW; Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Munoz L; Department of Pathology, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia.
  • Wei A; Department of Clinical Hematology, The Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
  • Ekert PG; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Pediatrics, University of Melbourne, Parkville, VIC 3050, Australia; Murdoch Children's Research Institute, Royal Children's H
  • Vaux DL; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Wong WW; Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
  • Silke J; Cell Signaling & Cell Death and Cancer & Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia. Electronic address: silke@wehi.edu.au.
Cancer Cell ; 29(2): 145-58, 2016 Feb 08.
Article en En | MEDLINE | ID: mdl-26859455
Birinapant is a smac-mimetic (SM) in clinical trials for treating cancer. SM antagonize inhibitor of apoptosis (IAP) proteins and simultaneously induce tumor necrosis factor (TNF) secretion to render cancers sensitive to TNF-induced killing. To enhance SM efficacy, we screened kinase inhibitors for their ability to increase TNF production of SM-treated cells. We showed that p38 inhibitors increased TNF induced by SM. Unexpectedly, even though p38 is required for Toll-like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM. Hence, we show that the p38/MK2 axis can inhibit or promote TNF production, depending on the stimulus. Importantly, clinical p38 inhibitors overcame resistance of primary acute myeloid leukemia to birinapant.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Leucemia / Proteínas Serina-Treonina Quinasas / Imitación Molecular / Proteínas Mitocondriales / Proteínas Quinasas p38 Activadas por Mitógenos / Péptidos y Proteínas de Señalización Intracelular / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Australia
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Leucemia / Proteínas Serina-Treonina Quinasas / Imitación Molecular / Proteínas Mitocondriales / Proteínas Quinasas p38 Activadas por Mitógenos / Péptidos y Proteínas de Señalización Intracelular / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Australia