Daoud, Mila ORCID: 0000-0002-8705-5869, Broxtermann, Pia Nora, Schorn, Fabian, Werthenbach, J. Paul, Seeger, Jens Michael, Schiffmann, Lars M., Brinkmann, Kerstin ORCID: 0000-0002-9411-6674, Vucic, Domagoj ORCID: 0000-0003-3614-8093, Tuting, Thomas, Mauch, Cornelia, Kulms, Dagmar, Zigrino, Paola and Kashkar, Hamid (2022). XIAP promotes melanoma growth by inducing tumour neutrophil infiltration. EMBO Rep., 23 (6). HOBOKEN: WILEY. ISSN 1469-3178

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Daoud, MilaUNSPECIFIEDorcid.org/0000-0002-8705-5869UNSPECIFIED
Broxtermann, Pia NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schorn, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werthenbach, J. PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeger, Jens MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiffmann, Lars M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinkmann, KerstinUNSPECIFIEDorcid.org/0000-0002-9411-6674UNSPECIFIED
Vucic, DomagojUNSPECIFIEDorcid.org/0000-0003-3614-8093UNSPECIFIED
Tuting, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauch, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kulms, DagmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zigrino, PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kashkar, HamidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-684402
DOI: 10.15252/embr.202153608
Journal or Publication Title: EMBO Rep.
Volume: 23
Number: 6
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1469-3178
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; X-LINKED INHIBITOR; APOPTOSIS PROTEIN; METASTATIC MELANOMA; CELL-DEATH; CANCER; EXPRESSION; FAMILY; INFLAMMATION; ACTIVATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68440

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