Yair Elisha

Screening for genes involved in collective cell migration

(With Sabina Winograd-Katz)

The process of cell migration is important in diverse physiological and pathological processes such as development, immune surveillance and cancer metastasis. Cell migration at the single-cell level has been studied extensively over many decades. Collective cell migration is the second principal mode of cell movement, particularly prevalent during embryogenesis, where it drives the formation of complex tissues. This type of migration, also known as “invasion,” characterizes many invasive tumors. During collective cell migration, the cells remain physically and functionally connected, and the integrity of cell-cell junctions is preserved during movement. Multicellular polarity and organization of the actin cytoskeleton generate traction and protrusion force for migration. In most modes of collective cell migration, moving cell groups modify the tissue along the migratory path (e.g., ECM modification and deposition of basement membrane). In order to better understand the process of collective cell migration and to find novel genes involved in this process, we will perform an siRNA screen. Genes found to affect collective cell migration will be assayed for their involvement in other cancer cell types, and we will further analyze their mechanism of action. We believe that this project could lead to new therapeutic targets for cancer cell invasion.

Figure Legend

4T1 cells were seeded in a multi-well plate, and the monolayer was wounded. Cells were allowed to migrate for 5 hrs, and then stained for actin (phalloidin-blue) and beta-catenin (yellow). The image is a montage of 25 images.

Inserts: 4T1 cells were stainded for vinculin (green), actin (phalloidin-red), and beta-catenin (blue). Scale bar: 10µm.