Croatian science foundation project (IP-2019-04-5382)  Cancer-related genes in sponges (CanSponGE).

Schematic illustration of described sponge homologs of human cancer-related genes/proteins and cancer-associated processes (Cetkovic et al, 2018).

The use of animals as experimental models for human diseases is imperative for understanding the causes, biology, and prevention of diseases.

To date, little is known about the functions of cancer-related genes in invertebrates, especially in non-bilaterian Metazoa. In the last few years, the interest in genes associated with cancer from an evolutionary perspective is increasing, since it has been shown that many of them were already present in simple non-bilaterian animals. The majority of these genes appeared in two major evolutionary transitions - the emergence of eukaryotes and the transition to multicellularity in the animal lineage.

Therefore, studying cancer-related genes in organisms at the base of Metazoa, such as sponges, can help to unravel the original function as well as the evolution of those genes. Sponges are morphologically simple animals, with no tissues and organs, which have changed little during evolution. Despite that, sponges possess complex genomes with many genes highly similar to their vertebrate homologs. Therefore, they provide an invaluable insight into the metazoan last common ancestors’ genome and proteome features.

The aim of the proposed project is to identify and characterize sponge homologs of human cancer-related genes and thus gain a clearer picture of the evolution of cancer. Such innovative approach using a simple model system will provide insights into the original ancestral physiological functions of cancer-related genes before their diversification and specialization in "higher" animals.

Our understanding of the basic physiological properties of cancer-related genes in simple animals will aid in unravelling complex interactions of their human homologs and thus elucidate possible causes of their oncogenic potential. Due to the "basal" phylogenetic position of sponges within animals, new insights in the properties of their cancer-related homologs will substantially improve our understanding of this disease.

Publications

• Talajić, A., Dominko, K., Lončarić, M., Ambriović-Ristov, A., Ćetković, H. The ancestral type of the R-RAS protein has oncogenic potential. Cellular & Molecular Biology Letters (2024) 29, 27. https://doi.org/10.1186/s11658-024-00546-0
• Dominko, K., Talajić, A., Radić, M., Vidaček, N.Š., Vlahoviček, K., Bosnar, M.H., Ćetković, H. Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins. (2023) Marine Drugs 21, 119. https://doi.org/10.3390/md21020119
• Beljan, S., Dominko, K., Talajić, A., Hloušek‑Kasun, A., Škrobot Vidaček, N., Herak Bosnar, M.,Vlahoviček, K., Ćetković, H. Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans. Sci Rep 12, 2022, 11379. https://doi.org/10.1038/s41598-022-15242-2
• Proust, B., Radić, M., Vidaček, N. Š., Cottet, C., Attia, S., Lamarche, F., Ačkar, L., Mikulčić, V. G., Tokarska-Schlattner, M., Ćetković, H., Schlattner, U., & Bosnar, M. H. NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix. Cell & bioscience, 11(1), 2021, 195.
• Filić, V., Mijanović, L., Putar, D., Talajić, A., Ćetković, H., & Weber, I., Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom., Cells, 10(7), 2021, 1592.
• Beljan, Silvestar; Herak Bosnar, Maja; Ćetković, Helena. 2020. "Rho Family of Ras-Like GTPases in Early-Branching Animals" Cells 9, no. 10: 2279. https://doi.org/10.3390/cells9102279

Doctoral thesis

• Beljan, Silvestar 2022. "Evolutionary, biochemical and biological characterization of sponge Eunapius subterraneus DRG1 protein" University of Zagreb, Faculty of Science

Diploma thesis

• Modrić, Matea 2020. "Characterization of sponge Eunapius subterraneus DRG1 protein" University of Zagreb, Faculty of Science
• Lazarin, Leonarda 2023. "Biochemical characterization of the RRAS2 protein from the sponge Eunapius subterraneus" University of Zagreb, Faculty of Science

Associates

• Kristina Dominko, PhD, Ruđer Bošković Institute
• Antea Talajić, PhD student, Ruđer Bošković Institute
• Maja Herak Bosnar, PhD, Ruđer Bošković Institute
• Matija Harcet,  PhD, Ruđer Bošković Institute
• Andreja Mikoč , PhD, Ruđer Bošković Institute
• Nikolina Škrobot Vidaček, PhD, Ruđer Bošković Institute
• Helena Bilandžija,  PhD, Ruđer Bošković Institute
• Kristian Vlahoviček, PhD, Faculty of Science, University of Zagreb
• Silvestar Beljan, PhD, Faculty of Science, University of Zagreb