During wound healing and cancer metastasis, cells are frequently observed to migrate together in collective groups. Collective cell migration involves a complex interplay between growth factors and cell-cell interactions. The mechanisms that govern the collectiveness of epithelial cell migration remain poorly defined. We are interested in how different cell migration guiding signals are produced and sensed to yield distinct cell movement behavior. Using an array of live cell fluorescent biosensors and mathematical modeling, we are identifying the molecular mechanisms that may explain the collectiveness of epithelial sheet movement in response to growth factor stimulation. We showed that spatial constrained growth factor signaling at the leading edge of an epithelial sheet enables wound directed collective migration. Cell adherens junctions restrain individual cell migration but promote growth factor-induced collective migration. Disruption of the actin cytoskeleton or loss of adherens junctions activates autocrine EGFR signaling via TACE and elevated autocrine signaling increases cell proliferation and motility. The relevance of these findings for designing novel therapeutic approaches will be discussed.