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RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS

RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investig...

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Autores principales: Wang, Z, Zhou, Y, Hu, X, Chen, W, Lin, X, Sun, L, Xu, X, Hong, W, Wang, T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632296/
https://www.ncbi.nlm.nih.gov/pubmed/26469971
http://dx.doi.org/10.1038/cddis.2015.266
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author Wang, Z
Zhou, Y
Hu, X
Chen, W
Lin, X
Sun, L
Xu, X
Hong, W
Wang, T
author_facet Wang, Z
Zhou, Y
Hu, X
Chen, W
Lin, X
Sun, L
Xu, X
Hong, W
Wang, T
author_sort Wang, Z
collection PubMed
description RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, whereas the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA.
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spelling pubmed-46322962015-11-16 RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS Wang, Z Zhou, Y Hu, X Chen, W Lin, X Sun, L Xu, X Hong, W Wang, T Cell Death Dis Original Article RILP (Rab7-interacting lysosomal protein) is a key regulator for late endosomal/lysosomal trafficking, and probably a tumor suppressor in prostate cancer. However, the role of RILP in other cancers and the underlying mechanism for RILP in regulating the invasion of cancer cells remain to be investigated. In this study, we showed that overexpression of RILP in breast cancer cells inhibits the migration and invasion, whereas the depletion of RILP by RNAi-mediated knockdown promotes the migration and invasion. We identified RalGDS (Ral guanine nucleotide dissociation stimulator) as a novel interacting partner for RILP, and truncation analysis revealed the N-terminal region of RILP is responsible for interacting with the guanine nucleotide exchange factor (GEF) domain of RalGDS. Immunofluorescence microscopy revealed that RalGDS can be recruited to the late endosomal compartments by RILP. Further investigations indicated that the overexpression of RILP inhibits the activity of RalA, a downstream target of RalGDS. Our data suggest that RILP suppresses the invasion of breast cancer cells by interacting with RalGDS to inhibit its GEF activity for RalA. Nature Publishing Group 2015-10 2015-10-15 /pmc/articles/PMC4632296/ /pubmed/26469971 http://dx.doi.org/10.1038/cddis.2015.266 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Wang, Z
Zhou, Y
Hu, X
Chen, W
Lin, X
Sun, L
Xu, X
Hong, W
Wang, T
RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title_full RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title_fullStr RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title_full_unstemmed RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title_short RILP suppresses invasion of breast cancer cells by modulating the activity of RalA through interaction with RalGDS
title_sort rilp suppresses invasion of breast cancer cells by modulating the activity of rala through interaction with ralgds
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632296/
https://www.ncbi.nlm.nih.gov/pubmed/26469971
http://dx.doi.org/10.1038/cddis.2015.266
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