1. Synthetic dysmobility

It is interesting how different signalling pathways coordinate with each other to establish distinct cell migration modules including polarity, motility, cell-matrix adhesion, and cell-cell coordination. To address this question, we conducted a “synthetic dysmobility” cell migration screen by doubly hitting human umbilical vein endothelial cells (HUVECs) with an shRNA and a small molecule inhibitor targeting different pathways. Then collective cell migration assays were utilized to identify synergistic or antagonistic interactions between these two hits. Candidate interaction pairs were further verified in different cancer cell lines. Single-cell tracing was also employed to elucidate how cell migration patterns of speed, directionality, persistence , and coordination were altered in these interaction pairs. With clear understanding of synthetic signalling interactions, we will develop novel therapeutic strategies against cell migration-related disease processes including angiogenesis, wound healing & cancer metastasis.