RhoGDI2 is associated with HGF-mediated tumor invasion through VEGF in stomach cancer

Title
RhoGDI2 is associated with HGF-mediated tumor invasion through VEGF in stomach cancer
Author(s)
이경희고성애김민경김상운김재룡
Keywords
GDP-DISSOCIATION INHIBITOR; GROWTH-FACTOR; RHO-GTPASES; SIGNAL-TRANSDUCTION; CELL BIOLOGY; LY-GDI; ANGIOGENESIS; METASTASIS; MECHANISMS; EXPRESSION
Issue Date
201410
Publisher
SPRINGER
Citation
CLINICAL & EXPERIMENTAL METASTASIS, v.31, no.7, pp.805 - 815
Abstract
RhoGDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of tumor metastasis; however, its role in cancer remains controversial. The aims of this study were to analyze RhoGDI2 in gastric cancer growth and metastasis, and to determine its possible signaling pathway. The level of expression of RhoGDI2 was further confirmed by real time RT-RCR and Western blot analysis. Transfection of cells with RhoGDI2 shRNA resulted in no effects of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with RhoGDI2 shRNA, compared with control cells, were able to invade across a Matrigel membrane barrier. The role of RhoGDI2 in the level of HGF-induced up-regulation of vascular endothelial growth factor (VEGF) was measured by knockdown of RhoGDI2 with RhoGDI2 shRNA and a chromatic immuno-precipitation assay. The levels of RhoGDI2 and VEGF were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up-regulation of VEGF was repressed by RhoGDI2 knockdown. HGF-induced upregulation of phosphorylated ERK and P38 levels was inhibited in RhoGDI2 knockdown cells. HGF enhanced the binding activity of RhoGDI2 to the VEGF promoter in control cells, but not in RhoGDI2-shRNA cells. Findings of this study also showed a statistically significant difference in the mean RhoGDI2 level before and after surgery (p < 0.01) and the mean level of RhoGDI2 before surgery showed a statistically significant difference depending on lymphatic, neural invasion and stage (p < 0.05). In conclusion, RhoGDI2 might play an important role in up-regulation of VEGF induced by HGF and contributes to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.
URI
http://hdl.handle.net/YU.REPOSITORY/30634http://dx.doi.org/10.1007/s10585-014-9671-4
ISSN
0262-0898
Appears in Collections:
의과대학 > 내과학교실 > Articles
의과대학 > 성형외과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
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