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

Emergent collective behavior plays an important role during cancer progression. Multiple studies suggest that cell groups are more likely to form clinically dangerous metastatic tumors. Prior in vitro work has found disrupted collective behavior in tumorigenic cells, but the connection between this behavior and in vivo tumorigenicity is unclear. Here we measure a multidimensional migration phenotype for a genetically defined experimental model of breast cancer. Using cells with controlled mutations, we find that PTEN deletion enhances collective migration. We also find that Ras activation suppresses collective behavior, even when combined with PTEN deletion. Both PTEN deletion and Ras activation are frequently found in cancer patients and the opposing effects of these two mutations on emergent behavior could be exploited in the development of novel treatments for metastasis. Our multidimensional characterization of emergent collective behavior is based on label-free imaging and thus could be applied to patient tumor samples for clinical assessments of metastatic potential.