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XIAP promotes melanoma growth by inducing tumour neutrophil infiltration
Author(s) -
Daoud Mila,
Broxtermann Pia Nora,
Schorn Fabian,
Werthenbach J Paul,
Seeger Jens Michael,
Schiffmann Lars M,
Brinkmann Kerstin,
Vucic Domagoj,
Tüting Thomas,
Mauch Cornelia,
Kulms Dagmar,
Zigrino Paola,
Kashkar Hamid
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202153608
Subject(s) - center of excellence , excellence , library science , university hospital , medicine , political science , computer science , law , family medicine
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.