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

Authors :
Jin-Man Kim
Chang Gyo Park
Bo Young Jeong
Yun Yong Park
Gordon B. Mills
Sun Young Rha
Kang Jin Jeong
Hoi Young Lee
Jae Ho Cheong
Kyung Hwa Cho
Source :
Experimental & Molecular Medicine. 50:e435-e435
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

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.

Details

ISSN :
20926413 and 12263613
Volume :
50
Database :
OpenAIRE
Journal :
Experimental & Molecular Medicine
Accession number :
edsair.doi...........0b9f2b0d8b3455bd1bf6a741b3a2d82a