Validation of Role of bin3 as a tumor suppressor that antagonizes the function of oncoprotein Yorkie

Abstract

Evidence suggests that cancer is a multistep process. Of these processes, activation of oncogenes and loss of tumor suppressors play a significant role in tumorigenesis. Yorkie/YAP signalling pathway has been well-studied and implicated in organ size control and tumorigenesis. However, there might be several unidentified genes which act as tumor suppressors that regulate the oncogenic function of Yorkie. To identify such genes, we performed a large scale-RNAi screen using Drosophila melanogaster as a model organism. In this screen, we identified bin3 as a potential tumor suppressor wherein, Yorkie overexpression leads to overgrowth of wing imaginal discs and loss of bin3 enhances this phenotype. The characterisation of these overgrown wing discs was performed to confirm several well-described hallmarks of cancer such as replicative immortality, evasion of apoptosis and metastatic nature. To understand the underlying pathway that leads to tumorigenesis, a hypothesis was proposed which investigates the role of Bin3 as a tumor suppressor that regulates the levels of Dpp target genes by regulating the levels of active Cdk9. Genetic rescue experiments and immunostainings were performed to validate the involvement of Cdk9. Furthermore, we have observed that there is increased nuclear localization of Yorkie when bin3 is knocked down, mechanism for which needs further investigation. Validation of these results in mammalian system is of future interest.