Universität zu Köln

Daoud, Mila ORCID: 0000-0002-8705-5869 (2022). XIAP promotes melanoma growth by inducing tumour neutrophil infiltration. PhD thesis, Universität zu Köln.

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Abstract

X-linked inhibitor of apoptosis (XIAP) is a member of the inhibitors of apoptosis proteins (IAPs) and it negatively regulates apoptosis via direct interaction and inhibition of caspase activity. XIAP expression is highly increased in malignant melanoma, thus XIAP was considered to mediate apoptosis resistance and therefore promotes melanoma progression. In addition to XIAP anti-apoptotic function, XIAP is involved in inflammatory responses and can induce NFκB activation. However, the inflammatory function of XIAP is still not considered in cancer. Our data show that XIAP supports melanoma tumour growth independently of its anti-apoptotic function. Moreover, XIAP mediates chemokine secretion like IL8, which mediates neutrophil chemo-attraction. Furthermore, our data reveal that XIAP forms a signalling complex with RIPK2 and TAB1. The XIAP-RIPK2-TAB1 complex mediates chemokine secretion and intra-tumoural neutrophil infiltration. Finally, deficiency of XIAP-RIPK2-TAB1 complex or depletion of neutrophils reduced melanoma growth in mice. Collectively, our data revealed a major signalling pathway that mediates melanoma growth and thus, identifies XIAP as a novel therapeutic target in cancer by targeting its inflammatory function.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Daoud, Mila mila.daoud@uk-koeln.de orcid.org/0000-0002-8705-5869 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-631519
Date:	2022
Place of Publication:	Cologne
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language XIAP English Melanoma English RIPK2 English
Date of oral exam:	15 August 2022
Referee:	Name Academic Title Kashkar, Hamid Prof
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/63151