Location, location, location: Melanoma cells "living at the edge".

Abnormal cell migration and invasion underlie metastatic dissemination, one of the major challenges for cancer treatment. Melanoma is one of the deadliest and most aggressive forms of skin cancer due in part to its migratory and metastatic potential. Cancer cells use a variety of migratory strategies regulated by cytoskeletal remodelling. In particular, we discuss the importance of amoeboid invasive melanoma strategies, since they have been identified at the edge of human melanomas. We hypothesize that the presence of amoeboid melanoma cells will favour tumor progression since they are invasive and metastatic; they support immunosuppression; they harbour cancer stem cell properties and they are involved in therapy resistance. The Rho-ROCK-Myosin II pathway is key to maintain amoeboid melanoma invasion but this pathway is further regulated by pro-tumorigenic/pro-metastatic/pro-survival signalling pathways such as JAK-STAT3, TGFβ-SMAD, NF-κB, Wnt11/5-FDZ7 and BRAFV600E -MEK-ERK. These pathways support amoeboid behaviour and are actionable in the clinic. After melanoma wide surgical margin removal, we propose that possible remaining melanoma cells should be eradicated using anti-amoeboid therapies.