Main findings
Cancer is characterized by the ability of cells to adapt and survive under various stress conditions within the tumor microenvironment (TME). One crucial cellular response to these stresses in normal cells which is ‘hijacked’ in cancer cells is the Unfolded Protein Response (UPR), which plays a vital role in maintaining cellular homeostasis. However, consequences of UPR activation in cancer cells and how this may affect the TME has largely been unexplored.
In this thesis, I characterized the roles of two key proteins in the UPR pathway, IRE1α and PERK, for prostate cancer (PCa) tumor growth and TME remodeling. Through a variety of experimental approaches, I discovered molecular mechanisms underlying immune suppression and tumor growth in the PCa TME, suggesting potential therapeutic strategies to enhance immunotherapy approaches in PCa. I also developed unique cell lines to simultaneously track the activities of UPR pathways in the same cell, which revealed potential novel regulators of the UPR molecular network. Using these novel reporter lines and an in vivo genome-scale CRISPR screen, I uncovered new targets with potential therapeutic impact in PCa, possibly also in other cancers. In summary, this thesis provides novel mechanistic information on the functioning of the UPR with translational implications.
Trial lecture: The role of DNA repair processes in cancer and implications for treatment
Time and place: 26 Sep. 2023, 10:15 AM, Nucleus, Bikuben, Kristine Bonnevies hus
Adjudication committee
Professor Eric Chevet, INSERM (National Institute of Health and Medical Research), Rennes
Professor Peter Nelson, Fred Hutchinson Cancer Center, University of Washington
Professor Rafal Ciosk, Department of Biosciences, University of Oslo
Chair of defense
Professor Kristian Prydz, Department of Biosciences, University of Oslo
Supervisors
Professor Fahri Saatcioglu, Department of Biosciences, University of Oslo
Researcher Yang Jin, Department of Biosciences, University of Oslo
Professor Cinzia Anita Maria Progida, Department of Biosciences, University of Oslo