Rab coupling protein mediated endosomal recycling of N-cadherin influences cell motility
dc.contributor.author | Lindsay, Andrew J. | |
dc.contributor.author | McCaffrey, Mary W. | |
dc.contributor.funder | Science Foundation Ireland | |
dc.date.accessioned | 2018-07-30T10:30:31Z | |
dc.date.available | 2018-07-30T10:30:31Z | |
dc.date.issued | 2017 | |
dc.description.abstract | Rab coupling protein (RCP) is a Rab GTPase effector that functions in endosomal recycling. The RCP gene is frequently amplified in breast cancer, leading to increased cancer aggressiveness. Furthermore, RCP enhances the motility of ovarian cancer cells by coordinating the recycling of alpha 5 beta 1 integrin and EGF receptor to the leading edge of migrating cells. Here we report that RCP also influences the motility of lung adenocarcinoma cells. Knockdown of RCP inhibits the motility of A549 cells in 2D and 3D migration assays, while its overexpression enhances migration in these assays. Depletion of RCP leads to a reduction in N-cadherin protein levels, which could be restored with lysosomal inhibitors. Trafficking assays revealed that RCP knockdown inhibits the return of endocytosed N-cadherin to the cell surface. We propose that RCP regulates the endosomal recycling of N-cadherin, and in its absence N-cadherin is diverted to the degradative pathway. The increased aggressiveness of tumour cells that overexpress RCP may be due to biased recycling of N-cadherin in metastatic cancer cells. | en |
dc.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.citation | Lindsay, A. J. and McCaffrey, M. W. (2017) 'Rab coupling protein mediated endosomal recycling of N-cadherin influences cell motility', Oncotarget, 8(62), pp. 104717-104732. doi: 10.18632/oncotarget.10513 | en |
dc.identifier.doi | 10.18632/oncotarget.10513 | |
dc.identifier.endpage | 104732 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.issued | 62 | |
dc.identifier.journaltitle | Oncotarget | en |
dc.identifier.startpage | 104717 | |
dc.identifier.uri | https://hdl.handle.net/10468/6519 | |
dc.identifier.volume | 8 | |
dc.language.iso | en | en |
dc.publisher | Impact Journals | en |
dc.relation.project | info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/09/IN.1/B2629/IE/Functional analysis of the Rab11 and Rab14 GTPases and their associated proteins in eukaryotic membrane trafficking with potential identification of targets for therapeutic intervention in the treatment of human disease/ | |
dc.relation.uri | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10513&path[]=33218 | |
dc.rights | © 2017, Lindsay et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en |
dc.rights.uri | https://creativecommons.org/licenses/by/3.0/ | |
dc.subject | RCP | en |
dc.subject | Migration | en |
dc.subject | Epithelial-mesenchymal transition | en |
dc.subject | N-cadherin | en |
dc.subject | Endosomal recycling | en |
dc.title | Rab coupling protein mediated endosomal recycling of N-cadherin influences cell motility | en |
dc.type | Article (peer-reviewed) | en |
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