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Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
- 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.
- Subjects :
- 0301 basic medicine
Regulation of gene expression
Clinical Biochemistry
Snail
Biology
medicine.disease
Biochemistry
Metastasis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Downregulation and upregulation
030220 oncology & carcinogenesis
biology.animal
Cancer cell
Cancer research
biology.protein
medicine
Molecular Medicine
Ectopic expression
Signal transduction
Molecular Biology
Fascin
Subjects
Details
- ISSN :
- 20926413 and 12263613
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Experimental & Molecular Medicine
- Accession number :
- edsair.doi...........0b9f2b0d8b3455bd1bf6a741b3a2d82a