Cancer Metastasis

Cancer metastasis involve a series of sequential steps: i) epithelial-to-mesenchymal transition (EMT) of individual cells within the primary tumor leading to their intravasation, ii) systemic survival of such circulating tumor cells (CTCs) and, finally, iii) their ability for extravasation at distant sites, where mesenchymal-to-epithelial transition (MET) potentiates their proliferation into metastatic lesions. Historically, EMT has been shown to be crucial for invasive and circulating cancer cells. However, it has been recently debated whether it plays actually a role for metastatic establishment. In fact, there are reports proposing that metastasis can directly derive from tumor-derived epithelial micro-emboli that break off from primary tumors, lodging into distal capillaries, where they initiate metastatic growth. These observations are exposing the cancer research community to a novel perspective concerning the metastatic process, in which patients with epithelial cancers may have CTCs retaining adhesion that are able to achieve distant colonization. Accordingly, our own results and expertise led us to assume that proficient cell-cell adhesion is decisive to promote collective cell invasion, as well as survival of matrix-detached cancer cells, by inducing stem-like properties and by decreasing their oxidative stress, which will potentiate the success of the metastatic process. It is then the aim of the Cancer Metastasis group to understand how cell adhesion is involved in epithelial cancer metastasis, contributing towards the identification of new strategies to monitor this complex biological process and to hamper cell adhesion-mediated survival in metastatic cancer cells, as well as its associated molecular mechanisms. Using breast cancer as the main model of study, we are focusing our activity to answer the following questions: 1) How do alterations in cell adhesion during early EMT impact cell plasticity, invasive capacity and metastatic spreading? 2) How does cell adhesion, and its induced-signaling pathways, contribute to the invasion-metastasis cascade? 3) How do cancer cell clusters communicate with the metastatic microenvironment and how does this dynamic crosstalk coordinate and dictate colonization capacity?