The transition from non-invasive phenotype to invasive phenotype of tumor cells marks the switch from a benign tumor to a more malignant form of cancer. Understanding the mechanisms underlying this hallmark event, which enables tumor cells to invade through Extracellular matrix, is critical for discovering pathways and new targets to develop anti-metastatic strategies. The discovery of anti-metastatic agents that inhibit cancer cell motility has been hindered by a dearth of cell motility assays that are compatible with high–throughput screening.