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Rab25 augments cancer cell invasiveness through a beta1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin

Authors
 Bo Young Jeong  ;  Kyung Hwa Cho  ;  Kang Jin Jeong  ;  Yun-Yong Park  ;  Jin Man Kim  ;  Sun Young Rha  ;  Chang Gyo Park  ;  Gordon B Mills  ;  Jae-Ho Cheong  ;  Hoi Young Lee 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.50(1) : e435, 2018 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
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 beta1 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 beta1 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.
DOI
10.1038/emm.2017.248
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162247
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