XIAP promotes melanoma growth by inducing tumour neutrophil infiltration.

Autor: Daoud M; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Broxtermann PN; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Schorn F; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Werthenbach JP; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Seeger JM; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Schiffmann LM; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne, Germany., Brinkmann K; The Walter & Eliza Hall Institute of Medical Research (WEHI) and Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia., Vucic D; Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA, USA., Tüting T; Laboratory of Experimental Dermatology, Department of Dermatology, University Hospital Magdeburg, Magdeburg, Germany., Mauch C; Faculty of Medicine and University Hospital of Cologne, Department of Dermatology and Venereology, University of Cologne, Cologne, Germany., Kulms D; Department of Dermatology, Experimental Dermatology, TU-Dresden, Dresden, Germany.; National Center for Tumor Diseases Dresden, TU-Dresden, Dresden, Germany., Zigrino P; Faculty of Medicine and University Hospital of Cologne, Department of Dermatology and Venereology, University of Cologne, Cologne, Germany., Kashkar H; Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital of Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2022 Jun 07; Vol. 23 (6), pp. e53608. Date of Electronic Publication: 2022 Apr 19.
DOI: 10.15252/embr.202153608
Abstrakt: Elevated expression of the X-linked inhibitor of apoptosis protein (XIAP) has been frequently reported in malignant melanoma suggesting that XIAP renders apoptosis resistance and thereby supports melanoma progression. Independent of its anti-apoptotic function, XIAP mediates cellular inflammatory signalling and promotes immunity against bacterial infection. The pro-inflammatory function of XIAP has not yet been considered in cancer. By providing detailed in vitro analyses, utilising two independent mouse melanoma models and including human melanoma samples, we show here that XIAP is an important mediator of melanoma neutrophil infiltration. Neutrophils represent a major driver of melanoma progression and are increasingly considered as a valuable therapeutic target in solid cancer. Our data reveal that XIAP ubiquitylates RIPK2, involve TAB1/RIPK2 complex and induce the transcriptional up-regulation and secretion of chemokines such as IL8, that are responsible for intra-tumour neutrophil accumulation. Alteration of the XIAP-RIPK2-TAB1 inflammatory axis or the depletion of neutrophils in mice reduced melanoma growth. Our data shed new light on how XIAP contributes to tumour growth and provides important insights for novel XIAP targeting strategies in cancer.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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