Digital Public Defence: Rojyar Khezri
MSc Rojyar Khezri at Institute of clinical Medicine will be defending the thesis Host autophagy mediates organ wasting and nutrient mobilization for tumor growth for the degree of Philosophiae Doctor (PhD).
Photo: Afshin Alizadeh
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.
Digital Trial Lecture - time and place
- First opponent: Professor Jayanta Debnath, University of California, USA
- Second opponent: Professor Ruth Palmer, University of Gothenburg, Sweden
- Third member and chair of the evaluation committee: Professor William E. Louch, Institute for Clinical Medicine, University of Oslo
Chair of defence
Professor II Therese Sørlie, Institute of Clinical Medicine, University of Oslo
Associate Professor Tor Erik Rusten, Institute of Clinical Medicine, University of Oslo
The human body consists of organs with trillions of cells that need to stay healthy for decades in terms of cell number and cell function. One essential cellular mechanism for this is autophagy. During autophagy (self-eating) a part of the cytoplasm is captured in a double-membrane vesicle and degraded upon fusion with the lysosome. The cell uses autophagy during stress conditions, like nutrient deficiency, to recycle organelles and cytoplasm as amino acids, sugars and nucleotides released from the lysosome for energetic use or as cellular building blocks.
This work demonstrates that autophagy has a complex role in cancer. Using an in vivo animal tumor model in fruit flies (Drosophila melanogaster), we show that malignant RasV12;scrib-/- tumors induce autophagy in the tumor microenvironment and peripheral organs such as fat and muscle tissue. Locally, inflammatory signaling mediates autophagy induction in the tumor microenvironment that, in turn, supports the growth of neighboring tumor cells. Novel, micro-computed tomography and metabolic profiling reveal that tumors additionally stimulate systemic cachexia responses with progressive organ atrophy, loss of body mass, and metabolic reprogramming that result in loss of motility, anorexia and death. Mechanistically, autophagy mediates muscle wasting and mobilization of nutrients in the form of sugar and amino acids from host tissues. Strikingly, whole body pharmacological or genetic autophagy inhibition reverses muscle loss, morbidity and metabolic parameters. Direct stable isotope measurements reveal that autophagy does not only mediate organ wasting but also nutrient release from host organs, that is utilized for tumor growth. This reconciles the observation of autophagy activation during cancer cachexia in mammals and identifies autophagy as a possible end-stage treatment in humans.
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