RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes

RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1002/ijc.32064
Journal or Publication Title: International Journal of Cancer
Volume: 144
Number: 12
Page Range: pp. 3070-3085
Date: 2019
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1002/ijc.32064
ISSN: 0020-7136
Date Deposited: 21 Dec 2020 22:57
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.

Keywords: RAB27A; exosomes; invasion; melanoma; metastasis.

© 2018 UICC.

Creators:
Creators
Email
Guo, Dajiang
UNSPECIFIED
Lui, Goldie Y.L.
UNSPECIFIED
Lai, Siew Li
UNSPECIFIED
Wilmott, James S.
UNSPECIFIED
Tikoo, Shweta
UNSPECIFIED
Jackett, Louise A.
UNSPECIFIED
Quek, Camelia
UNSPECIFIED
Brown, Darren L.
UNSPECIFIED
Sharp, Danae M.
UNSPECIFIED
Kwan, Rain Y.Q.
UNSPECIFIED
Chacon, Diego
UNSPECIFIED
Wong, Jason H.
UNSPECIFIED
Beck, Dominik
UNSPECIFIED
Geldermalsen, Michelle
UNSPECIFIED
Holst, Jeff
UNSPECIFIED
Thompson, John F.
UNSPECIFIED
Mann, Graham J.
UNSPECIFIED
Scolyer, Richard A.
UNSPECIFIED
Stow, Jennifer L.
UNSPECIFIED
Weninger, Wolfgang
UNSPECIFIED
Haass, Nikolas K.
UNSPECIFIED
Beaumont, Kimberley A.
UNSPECIFIED
Last Modified: 21 Dec 2020 22:57
URI: https://eprints.centenary.org.au/id/eprint/200

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