Characterizing a Mutation in the Gene ire1 Using a Cooperative Tumor Model in Drosophila: Role of the Unfolded Protein Response in Cancer
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The endoplasmic reticulum (ER) is a subcellular organelle wherein the majority of protein folding occurs. Stress conditions in the ER result in accumulation of misfolded proteins. The cell restores ER homeostasis through triggering the unfolded protein response (UPR). ER stress and the UPR are implicated in numerous diseases including neurodegenerative disorders, diabetes, and cancer, but their significance in many cases remains to be validated in vivo. Drosophila melanogaster is an ideal model system to study the role of UPR in cancer because of the tools available for complex genetic manipulations. One neoplastic tumor model in Drosophila involves the cooperation between mutations of the tumor suppressor gene scribble (scrib) and the oncogene ras. This model recapitulates many features of mammalian cancer, such as clonal origin and invasiveness. In this project, we aim to study the role of the UPR in Drosophila tumorigenesis. We characterize a mutation in the ire1 gene which encodes a key signal transducing protein in the UPR pathways using the RasV12scrib-Drosophila tumor model. We show that ire1 mutation suppresses tissue growth in tumors cooperatively or separately induced by RasV12and scrib-, suggesting ire1 mutation may have a general tumor-suppressing effect. Finally, we assess whether our ire1 mutation is truly responsible for the phenotype by addressing the issue of a potential background mutation. These results suggest that ire1 signaling may have a crucial role in facilitating tumor growth. This study also provides a valuable entry point to investigating the role of UPR in tumorigenesis using in vivo models.
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Leng, Sining, "Characterizing a Mutation in the Gene ire1 Using a Cooperative Tumor Model in Drosophila: Role of the Unfolded Protein Response in Cancer" (2012). Senior Projects Spring 2012. 151.
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