engleski

Group I Nme proteins in transition to multicellularity

The appearance of multicellularity is directly linked to the origin of cancer. Even some of the simplest early branching non-bilaterian animals, such as cnidarians, develop tumours. Furthermore, cancer and cancer-like phenomena appear in other multicellular lineages. Metastatic potential has the highest influence on the lethality and prognosis of cancer. One of the crucial events that occurs during metastasis is the change in tumour cell adhesion properties. Precisely regulated cell adhesion is also one of the essential elements for the evolution of complex multicellularity. Therefore, the same molecular interactions are involved in the origin of multicellular organization and in the metastatic process. These interactions include genes that are recognized as metastasis suppressors in mammals. Human Nme1 is the first know and the most studied metastasis suppressor. In animals, Nme proteins are divided in Group I and Group II. Non-bilaterian animals have one or two Group I Nme proteins, and mammals have four. A vast majority of studies of Nme proteins focuses on human homologues due to their importance in biomedicine. We performed a series of tests and assays on two Nme Group I proteins – a homolog from a unicellular relative of animals - filasterean Capsaspora owczarcaki (NmeGp1Co), and a homolog from a demosponge Suberites domuncula (NmeGp1Sd). The aim was to compare the protein properties among them, and with the well known human Nme1 and Nme2 homologues in order to see how these properties changed with the transition to multicellularity, and subsequently in the evolution of complex animals. We found that the ancestral protein probably had most of the functions of the known mammalian homologues. Crucially, both sponge and filasterean proteins are able to suppress the migration potential of human cancer cells in vitro. However, there are differences in the biochemical properties of filasterean, sponge, and human proteins. Sponge protein demonstrates the condition before the duplications and specialisations in the vertebrate lineage. Differences between the filasterean and sponge proteins may be linked to the transition to multicelullarity.

Nme1, Porifera, FIlasterea, multicellularity

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