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Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin

The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular in...

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Autores principales: Jeong, Bo Young, Cho, Kyung Hwa, Jeong, Kang Jin, Park, Yun-Yong, Kim, Jin Man, Rha, Sun Young, Park, Chang Gyo, Mills, Gordon B, Cheong, Jae-Ho, Lee, Hoi Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799805/
https://www.ncbi.nlm.nih.gov/pubmed/29371698
http://dx.doi.org/10.1038/emm.2017.248
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author Jeong, Bo Young
Cho, Kyung Hwa
Jeong, Kang Jin
Park, Yun-Yong
Kim, Jin Man
Rha, Sun Young
Park, Chang Gyo
Mills, Gordon B
Cheong, Jae-Ho
Lee, Hoi Young
author_facet Jeong, Bo Young
Cho, Kyung Hwa
Jeong, Kang Jin
Park, Yun-Yong
Kim, Jin Man
Rha, Sun Young
Park, Chang Gyo
Mills, Gordon B
Cheong, Jae-Ho
Lee, Hoi Young
author_sort Jeong, Bo Young
collection PubMed
description The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.
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spelling pubmed-57998052018-02-21 Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin Jeong, Bo Young Cho, Kyung Hwa Jeong, Kang Jin Park, Yun-Yong Kim, Jin Man Rha, Sun Young Park, Chang Gyo Mills, Gordon B Cheong, Jae-Ho Lee, Hoi Young Exp Mol Med Original Article The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells. Nature Publishing Group 2018-01 2018-01-26 /pmc/articles/PMC5799805/ /pubmed/29371698 http://dx.doi.org/10.1038/emm.2017.248 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 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-nc-nd/4.0/
spellingShingle Original Article
Jeong, Bo Young
Cho, Kyung Hwa
Jeong, Kang Jin
Park, Yun-Yong
Kim, Jin Man
Rha, Sun Young
Park, Chang Gyo
Mills, Gordon B
Cheong, Jae-Ho
Lee, Hoi Young
Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title_full Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title_fullStr Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title_full_unstemmed Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title_short Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
title_sort rab25 augments cancer cell invasiveness through a β1 integrin/egfr/vegf-a/snail signaling axis and expression of fascin
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799805/
https://www.ncbi.nlm.nih.gov/pubmed/29371698
http://dx.doi.org/10.1038/emm.2017.248
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