Metastasis (Greek: displacement, Î¼ÎµÏ„Î¬=next + ÏƒÏ„Î¬ÏƒÎ¹Ï‚=placement, plural: metastases) is the transfer of a disease from one organ or part to another organ or part not directly connected with it. Only malignant tumor cells have the capacity to metastasize. Malignant cells can break away from a primary tumor, penetrate into lymphatic and blood vessels, circulate through the bloodstream, and grow in a distant focus (metastasize) in normal tissues elsewhere in the body. If the cancer spreads to other tissues and organs, it may decrease a patient's likelihood of survival.
Unfortunately, the treatment options currently available are rarely able to cure metastatic cancer. Indeed understanding how the malignant cells migrate from the primary tumour to colonize other tissues is an important issue to design an efficient therapy against cancer. In the past few years, two main modes of migration in a three-dimensional environment have been identified. Mesenchymal cells harbour an elongated morphology and degrade surrounding environment to metastasize. Amoeboid cells have a more round morphology and their movement is associated to the deformation of the cell body through the surrounding environment without degradation. The cell migration independently on the type is based on the cytoskeleton remodelling. The cytoskeleton is a "scaffolding" or "skeleton" contained, as all other organelles in the cell body. It is a dynamic structure that maintains cell shape and also enables cell motion. In fact, it is a bone-like structure floating around within the cytoplasm. Some proteins are directly involved in making the cytoskeleton and others participate in the cytoskeleton remodelling. Among this last family of proteins, the RHO-GTPases have been identified as key players of the cell migration. The aim of my postdoctoral project funded by the European Molecular Biology Organization was to identify the main regulators of the RHO-GTPases involved in the three-dimensional amoeboid migration and to understand how they work.