File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleRAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes
Authors
Issue Date2019
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal of Cancer, 2019, v. 144 n. 12, p. 3070-3085 How to Cite?
AbstractDespite 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.
Persistent Identifierhttp://hdl.handle.net/10722/267381
ISSN
2017 Impact Factor: 7.36
2015 SCImago Journal Rankings: 2.657

 

DC FieldValueLanguage
dc.contributor.authorGuo, D-
dc.contributor.authorLui, GYL-
dc.contributor.authorLai, SL-
dc.contributor.authorWilmott, JS-
dc.contributor.authorTikoo, S-
dc.contributor.authorJackett, LA-
dc.contributor.authorQuek, C-
dc.contributor.authorBrown, DL-
dc.contributor.authorSharp, DM-
dc.contributor.authorKwan, RYQ-
dc.contributor.authorChacon, D-
dc.contributor.authorWong, WHJ-
dc.contributor.authorBeck, D-
dc.contributor.authorvan Geldermalsen, M-
dc.contributor.authorHolst, J-
dc.contributor.authorThompson, JF-
dc.contributor.authorMann, GJ-
dc.contributor.authorScolyer, RA-
dc.contributor.authorStow, JL-
dc.contributor.authorWeninger, W-
dc.contributor.authorHaass, NK-
dc.contributor.authorBeaumont, KA-
dc.date.accessioned2019-02-18T09:00:50Z-
dc.date.available2019-02-18T09:00:50Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Cancer, 2019, v. 144 n. 12, p. 3070-3085-
dc.identifier.issn0020-7136-
dc.identifier.urihttp://hdl.handle.net/10722/267381-
dc.description.abstractDespite 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.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home-
dc.relation.ispartofInternational Journal of Cancer-
dc.rightsThis is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.titleRAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes-
dc.typeArticle-
dc.identifier.emailWong, WHJ: jwhwong@hku.hk-
dc.identifier.authorityWong, WHJ=rp02363-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.32064-
dc.identifier.hkuros296874-
dc.identifier.volume144-
dc.identifier.issue12-
dc.identifier.spage3070-
dc.identifier.epage3085-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats