RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells
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Hee Jun Cho1,*, Sun-Mi Park1,*, In-Kyu Kim1,*, In-Koo Nam1,*, Kyoung Eun Baek1, Min-Ju Im1, Jong-Min Yoo1, Seung-Ho Park1, Ki-Jun Ryu1, Hyun-Tak Han1, Hyo-Jin Kim1, Soon-Chan Hong2, Kwang Dong Kim1, Yunbae Pak1, Jae Won Kim1, Chang Won Lee1 and Jiyun Yoo1
1 Division of Applied Life Science (BK21 plus), Research Institute of Life Sciences, Gyeongsang National University, Jinju, Korea
2 Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, Korea
* These authors contributed equally to the work
Jiyun Yoo, email:
Keywords: RhoGDI2, EMT, Snail, gastric cancer, invasion
Received: December 23, 2013 Accepted: February 5, 2014 Published: March 30, 2014
Rho GDP dissociation inhibitor 2 (RhoGDI2) expression correlates with tumor growth, metastasis, and chemoresistance in gastric cancer. Here, we show that RhoGDI2 functions in the epithelial-mesenchymal transition (EMT), which is responsible for invasiveness during tumor progression. This tumorigenic activity is associated with repression of E-cadherin by RhoGDI2 via upregulation of Snail. Overexpression of RhoGDI2 induced phenotypic changes consistent with EMT in gastric cancer cells, including abnormal epithelial cell morphology, fibroblast-like properties, and reduced intercellular adhesion. RhoGDI2 overexpression also resulted in decreased expression of the epithelial markers E-cadherin and β-catenin and increased expression of the mesenchymal markers vimentin and fibronectin. Importantly, RhoGDI2 overexpression also stimulated the expression of Snail, a repressor of E-cadherin and inducer of EMT, but not other family members such as Slug or Twist. RNA interference-mediated knockdown of Snail expression suppressed RhoGDI2-induced EMT and invasion, confirming that the effect was Snail-specific. These results indicate that RhoGDI2 plays a critical role in tumor progression in gastric cancer through induction of EMT. Targeting RhoGDI2 may thus be a useful strategy to inhibit gastric cancer cell invasion and metastasis.
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