A survey of metastasis suppressors in Metazoa

Ćetković, Helena; Harcet, Matija; Roller, Maša; Bosnar, Maja Herak

doi:10.1038/s41374-018-0024-9

Cited by 10 publications

(7 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sponges are ancient animals and possibly the earliest branching animal phylum that has changed little over the last 800 million years [ 58 ]. Therefore, they provide important insights into the genomic and proteomic features of the last common ancestor of metazoans [ 59 , 60 , 61 ]. Despite their simple morphology, sponges have complex genomes [ 60 ] with many genes very similar to their vertebrate homologs [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins

et al. 2023

Self Cite

View full text Add to dashboard Cite

The determination of the protein’s intracellular localization is essential for understanding its biological function. Protein localization studies are mainly performed on primary and secondary vertebrate cell lines for which most protocols have been optimized. In spite of experimental difficulties, studies on invertebrate cells, including basal Metazoa, have greatly advanced. In recent years, the interest in studying human diseases from an evolutionary perspective has significantly increased. Sponges, placed at the base of the animal tree, are simple animals without true tissues and organs but with a complex genome containing many genes whose human homologs have been implicated in human diseases, including cancer. Therefore, sponges are an innovative model for elucidating the fundamental role of the proteins involved in cancer. In this study, we overexpressed human cancer-related proteins and their sponge homologs in human cancer cells, human fibroblasts, and sponge cells. We demonstrated that human and sponge MYC proteins localize in the nucleus, the RRAS2 in the plasma membrane, the membranes of the endolysosomal vesicles, and the DRG1 in the cell’s cytosol. Despite the very low transfection efficiency of sponge cells, we observed an identical localization of human proteins and their sponge homologs, indicating their similar cellular functions.

show abstract

Section: Introductionmentioning

confidence: 99%

Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since sponges branched-off at the base of the animal tree, they are important for studying ancestral metazoan homologs before their diversification and specialization in complex "higher" animals, providing a new approach in understanding numerous biological processes, including cancer development and progression [16][17][18][19][20] . Earlier studies have shown that sponge proteins are highly similar in primary, predicted secondary, and tertiary structures, to homologs in "higher" metazoans, suggesting similar or identical biochemical and biological functions 17,18,[21][22][23][24][25][26][27][28][29] . We have previously shown that at least some sponge proteins have biochemical and biological characteristics similar to their human homologs, including metastatic and/or tumor suppression properties [30][31][32][33] .…”

mentioning

confidence: 99%

Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans

Beljan

Dominko

Talajić

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.

show abstract

“…The phylogenetic tree and taxonomic groups were constructed based on literatures and Taxonomy Browser of National Center for Biotechnology Information (NCBI) (Cetkovic et al, 2018; Mukherjee and Brocchieri, 2013). The protein database of NCBI were searched to identify genes with orthologous proteins of Kif6 and Kif9 across a wide range of species (such as mammals, birds, amphibians, fishes, jawless vertebrates, cephalochordates, urochordates, echinoderms, nematodes, mollusks, flatworms, cnidarians, placozoans and protozoans) using the full-length murine protein sequences of Kif6 and Kif9 as queries.…”

Section: Methodsmentioning

confidence: 99%

Distinct Roles of Kif6 and Kif9 in Mammalian Ciliary Trafficking and Motility

Fang,

Pan,

et al. 2023

Preprint

View full text Add to dashboard Cite

Motile cilia composed of 9+2 axonemes generate coordinated beats to propel directional fluid flows for various physiological functions. This requires multiciliated cells to establish translational, rotational and planar polarities. However, the mechanism underlying the establishment of these polarities remain elusive. Here, we delve into the functions of mammalian kinesin-9 family and uncover that Kif6, but not Kif9, is critical for establishing both rotational and planar polarities. Kif6 associates with intraflagellar transport (IFT) pariticles and participates in IFT within motile cilia. Knockout of Kif6 leads to severe hydrocephalus due to disruptions in both rotational and tissue-level polarity across ependyma. Conversely, while Kif9 is proposed as a central pair kinesin, its depletion does not significantly affect ependymal cilia motility, although ventricular expansion and defective sperm motility are observed. These findings reveal the unique roles of Kif6 and Kif9 in regulating cilia/flagella beating, providing valuable insights into the complex regulatory mechanisms governing the polarity of multiciliated tissues and the motility of cilia/flagella.

show abstract

A survey of metastasis suppressors in Metazoa

Cited by 10 publications

References 137 publications

Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins

Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins

Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans

Distinct Roles of Kif6 and Kif9 in Mammalian Ciliary Trafficking and Motility

Contact Info

Product

Resources

About