engleski

Characterization of cancer-associated RRAS2 and BRMS1 homologs from the freshwater sponge Eunapius subterraneus

From an evolutionary perspective, cancer is a condition of multicellularity and differentiation. Studies suggest that many genes and pathways involved in tumorigenesis appeared at the emergence of multicellularity and early in the evolution of animals. Sponges (phylum Porifera) are diploblastic organisms with simple morphology that are among the most distant relatives of humans, yet, they possess complex genomes with many genes highly conserved to their vertebrates’ homologs. Thus, investigation of cancer-related genes in sponges provides a new approach in understanding their basic physiological functions and evolution. We identified homologs of the RRAS2 and BRMS1 in the freshwater sponge Eunapius subterraneus. RRAS2 (TC21) is a small GTPase with an important role in signal transduction that controls critical biological processes, including cell proliferation, migration and survival, which implies its oncogenic role. On the other side, BRMS1 is a member of the chromatin remodelling mammalian switch-independent 3 (mSin3) complex that has a role as a metastasis suppressor, since it significantly decreases migration, invasion and colony formation. In order to investigate their evolutionary conservation, we performed comprehensive phylogenetic analysis of RRAS2 and BRMS1. Our biological experiments demonstrated intracellular localization of exogenous sponge and human RRAS2 and BRMS1 in sponge cells, and in human normal and tumor cells. Furthermore, the role of sponge RRAS2 and BRMS1 in cell proliferation, migration and colony formation showed that they share cancer-related properties with their human homologs, indicating that their biological functions originated early in the metazoan evolution.

BRMS1 ; cancer ; evolution ; RRAS2

nije evidentirano