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Characterization of sponge homologs of human metastasis suppressors CSTA and DRG1

Cancer is regarded as a pathological state that leads to the formation of metastasis from a primary tumor mass. Research of ancestral homologs of cancer-related genes in human has gained more popularity in recent years since comparative genomic studies have confirmed that many homologs of human genes were already present in simple metazoans. From an evolutionary point of view, the development of cancer is most likely related to the development of multicellularity and the appearance of true tissues and organs. Even though sponges (Porifera) are morphologically simple animals, having only few cell types without true tissues and organs, their genomes are highly complex and include many genes homologous to the cancer- related genes in “higher” animals. Therefore, they provide an interesting model for studying ancestral homologs of cancer-related genes. Metastasis suppressors inhibit metastasis formation without affecting primary tumor growth. Bioinformatics analyses have shown that homologs of metastasis suppressors were probably already present in the last common ancestor of all animals. To better understand the basic role of ancestral metastasis suppressor homologs, we analyzed sponge homologs of the two main metastasis suppressor genes: cystatin A (CSTA) and developmentally-regulated GTP-binding protein 1 (DRG1). Our bioinformatics and phylogenetic analyses showed that these proteins are conserved across animals. Transfection of sponge and human cells revealed the intercellular localization of CSTA and DRG1 proteins. The proteins were then overexpressed in E. coli and confirmed by Western blot. Further biochemical and biological characterization is in progress. We believe that these results will provide a better understanding of the intracellular processes related to the metastasis suppression and pathology of cancer and metastasis.

sponges, cancer, CSTA, DRG1

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