@article {Lee2020.06.04.135178, author = {Rachel M. Lee and Michele I. Vitolo and Wolfgang Losert and Stuart S. Martin}, title = {Distinct Roles of Tumor-Associated Mutations in Collective Cell Migration}, elocation-id = {2020.06.04.135178}, year = {2020}, doi = {10.1101/2020.06.04.135178}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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 lines that range in their in vivo behavior from non-tumorigenic to aggressively metastatic. By using cells with controlled mutations, we show that PTEN deletion enhances collective migration, while Ras activation suppresses it, even when combined with PTEN deletion. These opposing effects on collective migration phenotype of two mutations that are frequently found in patient tumors could be exploited in clinical assessments of metastatic potential or in the development of novel treatments for metastatic disease.Competing Interest StatementThe PTEN-/- cells are licensed by Horizon Discovery Ltd. (Cambridge, UK). Dr. Vitolo receives compensation from the sale of these cells. The remaining authors declare no conflict of interest.}, URL = {https://www.biorxiv.org/content/early/2020/06/05/2020.06.04.135178}, eprint = {https://www.biorxiv.org/content/early/2020/06/05/2020.06.04.135178.full.pdf}, journal = {bioRxiv} }