Saposin-related gene function as tumor suppressor in tracheal system of Drosophila larvae via Hippo signaling pathway: Novel gene to gene network prediction with GeneMANIA

Abstract Saposin-related ( Sap-R ) proteins promote the hydrolases of sphingolipids in lysosomes. Disrupted human Sap-R functions may lead to death at an early age. More worse, effective therapeutics are not available due to poorly understood molecular underlying mechanisms. To gain more insights about these mechanisms, we utilized Drosophila melanogaster as a simple invertebrate model with available genetic tools, with special focus on larval stage to simulate the stage of infancy in human. We found that Sap-R localizes in inka cells of larval tracheal system. Down regulation of Sap-R using inka cells driver reduces the expression level of ecdyson triggering hormone without significant effect on ecdysis. Sap-R mutant larvae have reduced lysosomal function, disrupted tracheal cell-to-cell junctions, huge number of tracheal cells nuclei because of observed cell divisions. Moreover, reduced expression of Hippo signal transduction pathway key genes in Sap-R mutant trachea was confirmed theoretically and practically which may indicate the development of cancer. This initial study showed a relevant role of Sap-R signaling for suppressing airway cancer. Interfering with theoretically predicted pathways may provide novel therapeutic options in the future.