Exp Mol Med.
2018 Jan;50(1):e435. 10.1038/emm.2017.248.
Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin
- Affiliations
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- 1Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea. hoi@konyang.ac.kr
- 2Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 3Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 4Cancer Research Institute, Regional Cancer Center and Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea.
- 5Divison of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
- 6Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. jhcheong@yuhs.ac
- KMID: 2438365
- DOI: http://doi.org/10.1038/emm.2017.248
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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