Reconstrução do cenário evolutivo dos processos biológicos envolvidos no momento inicial da cascata metastática

Abstract

Metastasis is a complex and multifaceted process in which neoplastic cells spread from the primary tumor to other tissues, leading to the formation of secondary tumors. The evolutionary origin of genes associated with this process is still not fully explored, despite numerous analyses conducted to understand the biological mechanisms of metastasis. Given this gap, the aim of this work was to evaluate the evolution of orthologous genes associated with biological pathways implicated in the early stages of metastasis, including cell adhesion, cell junction organization, cell extravasation, epithelial-mesenchymal transition, and matrix metalloproteinase regulation. In our analysis, we reconstructed the evolutionary scenario by searching for 468 orthologous genes in 476 eukaryotic species. The last common ancestor (LCA) Human-Metamonada, Human-Choanoflagellata, and Human-Actinopterygii showed the highest number of gene rooting when compared to the respective previous taxa. The genes rooted in each of these ancestors are related to the complexity and gain of function of each of these taxa. In Human-Metamonada, genes related to cell motility mediated by cytoskeleton modulation were rooted, in Human-Choanoflagellata, genes regulating cell-cell and extracellular matrix adhesion were rooted, and finally, in Human-Actinopterygii, genes involved in cell extravasation and the major histocompatibility complex were predominantly rooted. Compared to previous knowledge, our analysis suggests that the complexity of metastatic mechanisms emerged progressively in different species throughout evolution. These findings provide new perspectives on the origin and evolution of metastatic mechanisms and highlight the importance of investigating the evolution of these genes for a better understanding of cancer progression. Continued research is essential to fill knowledge gaps and improve therapeutic interventions.