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EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1

Eph receptors and their corresponding ephrin ligands have been associated with regulating cell–cell adhesion and motility, and thus have a critical role in various biological processes including tissue morphogenesis and homeostasis, as well as pathogenesis of several diseases. Aberrant regulation of...

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Autores principales: Cho, H J, Hwang, Y-S, Yoon, J, Lee, M, Lee, H G, Daar, I O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814325/
https://www.ncbi.nlm.nih.gov/pubmed/29059157
http://dx.doi.org/10.1038/onc.2017.386
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author Cho, H J
Hwang, Y-S
Yoon, J
Lee, M
Lee, H G
Daar, I O
author_facet Cho, H J
Hwang, Y-S
Yoon, J
Lee, M
Lee, H G
Daar, I O
author_sort Cho, H J
collection PubMed
description Eph receptors and their corresponding ephrin ligands have been associated with regulating cell–cell adhesion and motility, and thus have a critical role in various biological processes including tissue morphogenesis and homeostasis, as well as pathogenesis of several diseases. Aberrant regulation of Eph/ephrin signaling pathways is implicated in tumor progression of various human cancers. Here, we show that a Rho family GTPase regulator, Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1), can interact with ephrinB1, and this interaction is enhanced upon binding the extracellular domain of the cognate EphB2 receptor. Deletion mutagenesis revealed that amino acids 327–334 of the ephrinB1 intracellular domain are critical for the interaction with RhoGDI1. Stimulation with an EphB2 extracellular domain-Fc fusion protein (EphB2-Fc) induces RhoA activation and enhances the motility as well as invasiveness of wild-type ephrinB1-expressing cells. These Eph-Fc-induced effects were markedly diminished in cells expressing the mutant ephrinB1 construct (Δ327–334) that is ineffective at interacting with RhoGDI1. Furthermore, ephrinB1 depletion by siRNA suppresses EphB2-Fc-induced RhoA activation, and reduces motility and invasiveness of the SW480 and Hs578T human cancer cell lines. Our study connects the interaction between RhoGDI1 and ephrinB1 to the promotion of cancer cell behavior associated with tumor progression. This interaction may represent a therapeutic target in cancers that express ephrinB1.
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spelling pubmed-58143252018-02-22 EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1 Cho, H J Hwang, Y-S Yoon, J Lee, M Lee, H G Daar, I O Oncogene Original Article Eph receptors and their corresponding ephrin ligands have been associated with regulating cell–cell adhesion and motility, and thus have a critical role in various biological processes including tissue morphogenesis and homeostasis, as well as pathogenesis of several diseases. Aberrant regulation of Eph/ephrin signaling pathways is implicated in tumor progression of various human cancers. Here, we show that a Rho family GTPase regulator, Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1), can interact with ephrinB1, and this interaction is enhanced upon binding the extracellular domain of the cognate EphB2 receptor. Deletion mutagenesis revealed that amino acids 327–334 of the ephrinB1 intracellular domain are critical for the interaction with RhoGDI1. Stimulation with an EphB2 extracellular domain-Fc fusion protein (EphB2-Fc) induces RhoA activation and enhances the motility as well as invasiveness of wild-type ephrinB1-expressing cells. These Eph-Fc-induced effects were markedly diminished in cells expressing the mutant ephrinB1 construct (Δ327–334) that is ineffective at interacting with RhoGDI1. Furthermore, ephrinB1 depletion by siRNA suppresses EphB2-Fc-induced RhoA activation, and reduces motility and invasiveness of the SW480 and Hs578T human cancer cell lines. Our study connects the interaction between RhoGDI1 and ephrinB1 to the promotion of cancer cell behavior associated with tumor progression. This interaction may represent a therapeutic target in cancers that express ephrinB1. Nature Publishing Group 2018-02-15 2017-10-23 /pmc/articles/PMC5814325/ /pubmed/29059157 http://dx.doi.org/10.1038/onc.2017.386 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ 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
Cho, H J
Hwang, Y-S
Yoon, J
Lee, M
Lee, H G
Daar, I O
EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title_full EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title_fullStr EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title_full_unstemmed EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title_short EphrinB1 promotes cancer cell migration and invasion through the interaction with RhoGDI1
title_sort ephrinb1 promotes cancer cell migration and invasion through the interaction with rhogdi1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814325/
https://www.ncbi.nlm.nih.gov/pubmed/29059157
http://dx.doi.org/10.1038/onc.2017.386
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