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RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes.
Guo, Dajiang; Lui, Goldie Y L; Lai, Siew Li; Wilmott, James S; Tikoo, Shweta; Jackett, Louise A; Quek, Camelia; Brown, Darren L; Sharp, Danae M; Kwan, Rain Y Q; Chacon, Diego; Wong, Jason H; Beck, Dominik; van Geldermalsen, Michelle; Holst, Jeff; Thompson, John F; Mann, Graham J; Scolyer, Richard A; Stow, Jennifer L; Weninger, Wolfgang; Haass, Nikolas K; Beaumont, Kimberley A.
Affiliation
  • Guo D; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Lui GYL; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Lai SL; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Wilmott JS; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Tikoo S; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Jackett LA; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Quek C; Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia.
  • Brown DL; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Sharp DM; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Kwan RYQ; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Chacon D; Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia.
  • Wong JH; Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
  • Beck D; Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia.
  • van Geldermalsen M; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
  • Holst J; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Thompson JF; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Mann GJ; The Centenary Institute, The University of Sydney, Newtown, NSW, Australia.
  • Scolyer RA; Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
  • Stow JL; Centre for Health Technologies and the School of Biomedical Engineering, University of Technology, Sydney, NSW, Australia.
  • Weninger W; Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
  • Haass NK; Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
  • Beaumont KA; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
Int J Cancer ; 144(12): 3070-3085, 2019 06 15.
Article in En | MEDLINE | ID: mdl-30556600
ABSTRACT
Despite recent advances in targeted and immune-based therapies, advanced stage melanoma remains a clinical challenge with a poor prognosis. 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 in vitro, and spontaneous metastasis in vivo. The reduced invasion phenotype was rescued by RAB27A-replete exosomes, but not RAB27A-knockdown exosomes, indicating that RAB27A is responsible for the generation of pro-invasive 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-invasive exosome population. These findings support RAB27A as a key cancer regulator, as well as a potential prognostic marker and therapeutic target in melanoma.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Exosomes / Rab27 GTP-Binding Proteins / Melanoma Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Int J Cancer Year: 2019 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Exosomes / Rab27 GTP-Binding Proteins / Melanoma Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Int J Cancer Year: 2019 Document type: Article Affiliation country: