64 Oral - Cell Division and Cell Growth
Friday April 08, 9:30 AM - 9:45 AM

Authors:
Abhishek Sharma; Savraj Grewal

Affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Canada

Keywords:
r. tumor suppressors and oncogenes; a. stress responses

Our cells and organs need oxygen from the air we breathe in order to survive and function. However, in certain disorders - such as stroke, heart disease and cancer - tissues are often deprived of oxygen. Drosophila larvae provide an excellent in vivo model to study adaptive responses to hypoxia as they have evolved to live in naturally low oxygen conditions. We previously identified two mechanisms that promote organismal hypoxia tolerance – activation of the FOXO transcription factor and Tsc1/2-mediated suppression of TOR kinase signaling. Here we examine how both mechanisms operate to control organ-level growth and proliferative adaptation to hypoxia. To do this we examined tsc and foxo function in the developing larval imaginal disc epithelial tissues. Cell clones mutant for both tsc1 and foxo show an overgrowth phenotype under normal growth conditions. We find that this overgrowth is exacerbated under hypoxia and leads to altered tissue patterning. Moreover, we also find that tsc1/foxo double mutant clones are susceptible to high amount of apoptosis as compared to their wildtype counterparts and that this cell death is also further exacerbated under hypoxic conditions. In contrast to loss of tsc1/foxo we see that clones overexpressing oncogene yorkie do not show enhanced growth under hypoxic conditions. We are currently exploring mechanisms by which hypoxia exposure enhances the overgrowth of tsc1/foxo mutant tissue. The behaviour of tsc1, foxo double mutant clones under hypoxia recapitulate various tumor phenotypes such as high proliferation and apoptosis. Hence our work will help uncover how hypoxia impacts tumor growth.