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Understanding the genes and cellular processes that drive progression and metastasis is critical for identifying new therapeutic strategies. Here, we found that the GTPase RAB27A was overexpressed in a subset of melanomas, which correlated with poor patient survival. Loss of RAB27A expression in melanoma cell lines inhibited 3D spheroid invasion and cell motility <jats:italic>in vitro<\/jats:italic>, and spontaneous metastasis <jats:italic>in vivo<\/jats:italic>. The reduced invasion phenotype was rescued by RAB27A\u2010replete exosomes, but not RAB27A\u2010knockdown exosomes, indicating that RAB27A is responsible for the generation of pro\u2010invasive exosomes. Furthermore, while RAB27A loss did not alter the number of exosomes secreted, it did change exosome size and altered the composition and abundance of exosomal proteins, some of which are known to regulate cancer cell movement. Our data suggest that RAB27A promotes the biogenesis of a distinct pro\u2010invasive exosome population. These findings support RAB27A as a key cancer regulator, as well as a potential prognostic marker and therapeutic target in melanoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijc.32064","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T10:38:21Z","timestamp":1545043101000},"page":"3070-3085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["RAB27A promotes melanoma cell invasion and metastasis <i>via<\/i> regulation of pro\u2010invasive exosomes"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-5854","authenticated-orcid":false,"given":"Dajiang","family":"Guo","sequence":"first","affiliation":[{"name":"The Centenary Institute, The University of Sydney  Newtown NSW Australia"},{"name":"Sydney Medical School The University of Sydney  Camperdown NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goldie 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