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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\u2010ROCK\u2010Myosin II pathway is key to maintain amoeboid melanoma invasion but this pathway is further regulated by pro\u2010tumorigenic\/pro\u2010metastatic\/pro\u2010survival signalling pathways such as JAK\u2010STAT3, TGF\u03b2\u2010SMAD, NF\u2010\u03baB, Wnt11\/5\u2010FDZ7 and BRAF<jats:sup>V600E<\/jats:sup>\u2010MEK\u2010ERK. 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\u2010amoeboid therapies.<\/jats:p>","DOI":"10.1111\/exd.14423","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T16:52:31Z","timestamp":1624985551000},"page":"82-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Location, location, location: Melanoma cells \u201cliving at the edge\u201d"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-4388","authenticated-orcid":false,"given":"Oscar","family":"Maiques","sequence":"first","affiliation":[{"name":"Barts Cancer Institute John Vane Science Building Queen Mary University of London London 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