Chan et al. investigated the mechanism by which loss of the Ser/Thr kinase LKB1 facilitates the invasion and metastasis of melanoma cells. Using scratch wound assays, which remove the extracellular matrix (ECM), they found that LKB1 null melanoma cells migrated into the wound, but null cells in which LKB1 was re-expressed (addback cells) aligned at the wound edge, suggesting that LKB1 might be involved in boundary sensing. Indeed, addback cells, but not LKB1 null cells, migrated towards ECM gradients (haptotaxis); both cell types migrated towards soluble chemical cues (chemotaxis). LKB1-mediated phosphorylation of MAP/microtubule affinity-regulating kinase(MARK) family members was essential for its role in haptotaxis, although the downstream targets of MARKs here are unidentified. Thus, the LKB1–MARK pathway is required for melanoma cell haptotaxis and its disruption may promote their invasion.