Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate professor Jean Farup, Aarhus University, Denmark
- Second opponent: Research Director Etienne Lefai, Université Clermont Auvergne, France
- Third member and chair of the evaluation committee: Associate Professor Johanne Egge Rinholm, University of Oslo
Chair of the Defence
Associate Professor Jean-Luc Boulland, University of Oslo
Principal Supervisor
Professor Jérôme Ruzzin, University of Oslo
Summary
Preserving skeletal muscle integrity is essential for a healthy life. This thesis investigates the mechanisms underlying skeletal muscle deterioration during physiological aging and cancer-associated cachexia, while also exploring the intrinsic capacity of skeletal muscle to suppress cancer cell proliferation.
Findings presented in this work demonstrate that the aryl hydrocarbon receptor (AHR) is required for skeletal muscle homeostasis. Myofiber AHR loss results in skeletal muscle decline in adult mice, while AHR activation with FICZ prevents dexamethasone induced atrophy by stimulating anabolic signaling and suppressing atrogene expression. Furthermore, myofiber AHR loss enhances breast cancer-induced muscle wasting in female mice, indicating that AHR protects skeletal muscle under catabolic stress.
In addition, the thesis presents an in vitro co-culture model in which C2C12 myotubes suppress breast cancer cell proliferation and induce a pseudohypoxic transcriptional program. Hypoxia further inhibits cancer cell outgrowth on myotubes, an effect not replicated by myotube-secreted factors alone.
Collectively, these findings identify AHR as a key regulator of muscle integrity and implicate hypoxia as a contributor of skeletal muscle cell’s resistance to cancer cell colonization.
Additional information
Contact the research support staff.