Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
Experimental & Molecular Medicine
; : e435-2018.
Article
em En
| WPRIM
| ID: wpr-739490
Biblioteca responsável:
WPRO
ABSTRACT
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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Índice:
WPRIM
Assunto principal:
Neoplasias Ovarianas
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Caramujos
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Biomarcadores
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Regulação para Cima
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Linhagem da Célula
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Proteínas de Ligação ao GTP
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Fator A de Crescimento do Endotélio Vascular
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Expressão Ectópica do Gene
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Pulmão
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Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2018
Tipo de documento:
Article