Two research teams from IRIC recently identified novel regulators of cell migration, an essential process in the development of metastatic tumors. The study from the team of Gregory Emery was conducted in collaboration with the team of Paul S. Maddox helps to better understand the mechanisms controlling the migration of groups of cells which could lead to the identification of new therapeutic targets that could be used to prevent metastasis. The results of the study were published in the scientific journal The Journal of Cell Biology.
In patients affected by solid tumors (i.e. cancers other than leukemia and lymphoma), 90% of the lethality comes from secondary tumors: the metastatic tumors. These tumors are initiated by cells that leave the original tumor, then move into the surrounding tissues and sometimes use the bloodstream to invade target tissues such as the liver or the lungs. There is growing evidence that tumor cells do not move individually but as a group during collective migration. Moreover, these cells preferentially colonize certain organs because they are attracted by specific signals emanating from them.
Models for studying the molecular details of collective migration are rare. With this in mind, the team of Gregory Emery uses the fruit fly Drosophila to study the migration of a group of cells (also called border cells) as it is one of the most powerful models to understand the molecular mechanisms of metastatic migration.
In a previous study, Gregory Emery’s team has shown that certain transport mechanisms within the border cells are necessary to maintain their movement in a specific direction. Specifically, this study demonstrated the role of two proteins of the “Rab” family, Rab5 and Rab11 in this process. These proteins serve as “switches” for certain stages of intracellular transport. These “switches” must continually turn “on” and “off” for intracellular transport to operate normally. It was therefore essential to identify the proteins that “turn on” and “turn off” Rab5 and Rab11 in this context.
By screening among all proteins that can inhibit the Rab proteins, Gregory Emery’s group recently identified two proteins playing this role in collective cell migration. While one of these proteins is known to be acting on Rab5 in some mammalian cells, another protein, called Evi5 was until now poorly characterized. With the help of Paul Maddox’s team, they developed an algorithm to measure the activity of Rab11 in vivo, that this protein is necessary to “turn off” Rab11.
It is interesting to note that one form of Rab11 is involved in the formation of metastatic tumors in breast cancer. Evi5 may therefore constitute a therapeutic target in this context. Furthermore, the “switches” Rab5 and Rab11 are important in many other signaling pathways between cells and implicated in many diseases. Understanding how the cycle of activity of these proteins is controlled is therefore of great importance.
Laflamme C, Assaker G, Ramel D, Dorn JF, She D, Maddox PS, Emery G. (2012). Evi5 promotes collective cell migration through its Rab-GAP activity. The Journal of Cell Biology (Epub 2012 July 3).