A sponge homolog of BRMS1 reveals ancient origin of metastasis-suppressing functions

Early-branching metazoans, such as sponges (Porifera), can provide valuable insight into the emergence of complex gene regulatory systems and cancer-related mechanisms in early metazoan evolution. BRMS1 (breast cancer metastasis suppressor 1) is a component of the Sin3-HDAC complex involved in chromatin remodeling and transcriptional regulation. In humans, BRMS1 inhibits cancer metastasis by modulating signaling pathways that control cell migration, adhesion, and proliferation. Despite its biomedical importance, the evolutionary origin and basic functions of BRMS1 remain largely unexplored.

We identified and characterized a BRMS1 homolog from the cave sponge Eunapius subterraneus and compared it with human BRMS1 and BRMS1-like paralogs. Phylogenetic analyses revealed that BRMS1 and BRMS1-like arose from a duplication of an ancestral BRMS1 gene during early vertebrate evolution. Structural modeling showed that sponge BRMS1 shares high similarity with human BRMS1. Co-immunoprecipitation assays demonstrated that sponge BRMS1 physically associates with human BRMS1 in mammalian cells. In both sponge and human cells, sponge BRMS1 localized predominantly to the nucleus, similar to human BRMS1 and BRMS1-like. Functional assays in human breast cancer cells revealed that sponge BRMS1 suppresses proliferation, colony formation, and migration to a degree comparable to its human homologs.

Our findings demonstrate that the key structural features, subcellular localization, and biological functions of BRMS1 are conserved between sponges and humans. The ability of a sponge BRMS1 homolog to integrate into human protein complexes and suppress cancer cell migration and proliferation suggests that fundamental BRMS1 activities arose early in metazoan evolution, independent of anatomical and functional complexity.