The major problems of cancer disease are 1) the relapse and resistance to current therapies that have been associated with the presence of cancer stem cells (CSCs) and 2) the spread of invasive metastatic cells to distant organs that is responsible for most cancer-associated deaths. CSCs represent a tumour cell subpopulation with the ability to self-renew and differentiate into non-CSCs. In carcinoma cells, the acquisition of stemness properties has been closely related to epithelial-mesenchymal transition (EMT), a key process in cancer invasion and metastasis. However, although EMT can be considered a process that generates CSCs, the connection between CSCs and metastasis is not yet well understood. Interestingly, in melanoma, a non-epithelial tumour, transition from elongated-mesenchymal to amoeboid mode of movement (MAT) driven by Rho-ROCK signalling has been associated with increased stemness. Nevertheless, how very contractile cells regulate genes involved in EMT, tumour initiation and metastatic spread remains unexplored. Moreover, it is not known if the same genes regulate all these processes. As increasing cellular plasticity via EMT in carcinoma cells or via MAT in melanoma cells correlates with increasing stemness, we hypothesized a molecular link between the pathways regulating both migration and stemness abilities. Therefore, the main goal of this proposal has been to understand how tumour cells can acquire stem cell traits to successfully metastasize and how this can be regulated by the actomyosin cytoskeletal by using an interdisciplinary approach that combines state-of-the-art techniques in molecular and cellular biology, biochemistry, in vivo imaging and animal models. This has allow us to identify key important genes regulating both stemness traits and metastatic spread and identified prognostic markers of distant relapse and patient survival.
