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

Guo, D; Lui, GYL; Lai, SL; Wilmott, JS; Tikoo, S; Jackett, LA; Quek, C; Brown, DL; Sharp, DM; Kwan, RYQ; Chacon, D; Wong, JH; Beck, D; van Geldermalsen, M; Holst, J; Thompson, JF; Mann, GJ; Scolyer, RA; Stow, JL; Weninger, W; Haass, NK; Beaumont, KA

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

Guo, D Lui, GYL Lai, SL Wilmott, JS Tikoo, S Jackett, LA Quek, C Brown, DL Sharp, DM Kwan, RYQ Chacon, D

Wong, JH Beck, D van Geldermalsen, M Holst, J Thompson, JF Mann, GJ Scolyer, RA Stow, JL Weninger, W Haass, NK Beaumont, KA

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Publication Type:: Journal Article
Citation:: International Journal of Cancer, 2019, 144 (12), pp. 3070 - 3085
Issue Date:: 2019-06-15

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Field	Value	Language
dc.contributor.author	Guo, D	en_US
dc.contributor.author	Lui, GYL	en_US
dc.contributor.author	Lai, SL	en_US
dc.contributor.author	Wilmott, JS	en_US
dc.contributor.author	Tikoo, S	en_US
dc.contributor.author	Jackett, LA	en_US
dc.contributor.author	Quek, C	en_US
dc.contributor.author	Brown, DL	en_US
dc.contributor.author	Sharp, DM	en_US
dc.contributor.author	Kwan, RYQ	en_US
dc.contributor.author	Chacon, D https://orcid.org/0000-0003-3729-1385	en_US
dc.contributor.author	Wong, JH	en_US
dc.contributor.author	Beck, D	en_US
dc.contributor.author	van Geldermalsen, M	en_US
dc.contributor.author	Holst, J	en_US
dc.contributor.author	Thompson, JF	en_US
dc.contributor.author	Mann, GJ	en_US
dc.contributor.author	Scolyer, RA	en_US
dc.contributor.author	Stow, JL	en_US
dc.contributor.author	Weninger, W	en_US
dc.contributor.author	Haass, NK	en_US
dc.contributor.author	Beaumont, KA	en_US
dc.date.available	2018-11-30	en_US
dc.date.issued	2019-06-15	en_US
dc.identifier.citation	International Journal of Cancer, 2019, 144 (12), pp. 3070 - 3085	en_US
dc.identifier.issn	0020-7136	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132569
dc.description.abstract	© 2018 UICC 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.	en_US
dc.relation.ispartof	International Journal of Cancer	en_US
dc.relation.isbasedon	10.1002/ijc.32064	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Spheroids, Cellular	en_US
dc.subject.mesh	Melanosomes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Melanoma	en_US
dc.subject.mesh	Melanoma, Experimental	en_US
dc.subject.mesh	Nevus	en_US
dc.subject.mesh	Skin Neoplasms	en_US
dc.subject.mesh	Neoplasm Invasiveness	en_US
dc.subject.mesh	Culture Media, Conditioned	en_US
dc.subject.mesh	Proteomics	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Exosomes	en_US
dc.subject.mesh	Gene Knockdown Techniques	en_US
dc.subject.mesh	HEK293 Cells	en_US
dc.subject.mesh	Clustered Regularly Interspaced Short Palindromic Repeats	en_US
dc.subject.mesh	rab27 GTP-Binding Proteins	en_US
dc.title	RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	144	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access	*
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	144	en_US

Abstract:

© 2018 UICC 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/132569