The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Click here to participate in the public defence
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Associate Professor Jessie Villaneuva, Wistar Institute, USA
- Second opponent: Assistant Professor Markus Heppt, Universitätsklinikum Erlangen, Germany
- Third member and chair of the evaluation committee: Professor Lars Eide, University of Oslo
Chair of the Defence
Associate Professor Tone Kristin Bergersen, University of Oslo
Principal Supervisor
Researcher Ana Slipicevic, Oslo University Hospital
Summary
The incidence of melanoma, the most aggressive form of skin cancer, has been increasing for decades, especially in the Nordic countries. Both genetic factors and the environment affect the risk of developing melanoma during lifetime. During the last decade, multiple novel susceptibility loci for melanoma have been identified through genome wide association studies (GWAS), however, most of them are still not functionally characterized. This understanding is absolutely crucial for developing new prevention strategies and therapeutic approaches.
The aim of this thesis was to investigate a biological function of a novel candidate gene for melanoma susceptibility – MX2 – in melanoma development and progression.
We analyzed whole transcriptome data of primary and metastatic melanomas and found that higher MX2 mRNA expression is a favorable prognostic factor for melanoma patient survival. We found that MX2 protein is downregulated in metastatic melanoma samples and overexpression of MX2 reduces PI3K/AKT pathway activity and inhibits melanoma cell growth both in vitro and in vivo. Additionally, MX2 is involved in the establishment of an interferon-induced transcriptional profile and downregulation of MX2 followed by IFNα treatment strongly impairs STAT1 activation. Furthermore, higher MX2 expression renders melanoma cells significantly more sensitive to targeted therapy drugs, while in melanocytes it increases UV sensitivity.
To conclude, the work presented in this thesis provides the first mechanistic clues of MX2 contribution to melanoma risk and tumor development.
Additional information
Contact the research support staff.