Distinct Roles of Tumor-Associated Mutations in Collective Cell Migration*

Recent evidence suggests that groups of cells are more likely to form clinically dangerous metastatic tumors, emphasizing the importance of understanding mechanisms underlying collective behavior. The emergent collective behavior of migrating cell sheets in vitro has been shown to be disrupted in tumorigenic cells but the connection between this behavior and in vivo tumorigenicity is unclear. Here we use particle image velocimetry to measure a multi-dimensional collective migration phenotype for genetically defined cell types that range in their in vivo behavior from non-tumorigenic to aggressively malignant. By using cells with controlled mutations, we show that Ras activation and PTEN deletion lead to opposing effects on collective migration, despite both mutations being frequently found in patient tumors.