Drosophila melanogaster as a model for the study of cancer and degenerative diseases: The functional study of DmelEMC1 gene and the genetic interactions with other EMC complex members

Abstract

The development of cancer is a multistep process involving mutations in components of signaling pathways, cell cycle and cell death. Recent studies demonstrate the power of D. melanogaster to study these processes; witch the disruption can result in diseases, including various human syndromes. The data from our laboratory show that the silencing of EMC1 in melanoma cells reduces the rate of proliferation, migration and cell survival in vitro and attenuates tumor growth in vivo. In addition, the breast tumor cells overexpressing the EMC1 enhance the cell proliferation and migration. The results of the doctoral student Carlos Couto (Couto et al, manuscript in preparation) described in D. melanogaster the high lethality of animals when the EMC1 RNAi is driven to myogenic cell line since they cannot emerge from the puparium. The flies that can leave the pupae case are unable to fly, present severe morphological changes in their mitochondria, with the reduction in its oxygen consumption, leading to locomotor difficulty and a drastic decrease in the animal life span. The endogenous protein EMC1 was located in the sarcoplasmic reticulum, particularly concentrated in regions where the cisterns of the sarcoplasmic reticulum comprise mitochondria, which strengthens the role of EMC1 in the interconnection between endoplasmic reticulum and mitochondria. In this context, given the versatility in addressing various issues related to cancer biology and the demonstration of its direct relevance in tumorigenesis in mammals, we intend to use the advantages of this model to explore the molecular mechanisms of the DmelEMC1 protein participation in functional pathways, interaction between DmelEMC1 and the other members of the complex and the essential processes for tumor progression with the perspective to transfer the knowledge to the field of human cancer and human degenerative diseases.