RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells
| Autor: | Chang-Won Lee, Kyoung Eun Baek, Soon-Chan Hong, Seung-Ho Park, In-Kyu Kim, Jiyun Yoo, Jae-Won Kim, Min-Ju Im, Sun-Mi Park, Hee Jun Cho, Yunbae Pak, Hyo Jin Kim, Kwang Dong Kim, Jong-Min Yoo, In-Koo Nam, Ki-Jun Ryu, Hyun-Tak Han |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Epithelial-Mesenchymal Transition
Blotting Western Fluorescent Antibody Technique Vimentin Antineoplastic Agents Apoptosis Snail Real-Time Polymerase Chain Reaction Metastasis RhoGDI2 rho Guanine Nucleotide Dissociation Inhibitor beta Cell Movement Stomach Neoplasms biology.animal medicine Tumor Cells Cultured Humans Epithelial–mesenchymal transition RNA Messenger RNA Small Interfering Cell Proliferation biology Reverse Transcriptase Polymerase Chain Reaction gastric cancer EMT Cancer medicine.disease invasion Cadherins Molecular biology Oncology Tumor progression Drug Resistance Neoplasm Cancer cell biology.protein Abnormal Epithelial Cell Snail Family Transcription Factors Research Paper Transcription Factors |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Hee Jun Cho 1,* , Sun-Mi Park 1,* , In-Kyu Kim 1,* , In-Koo Nam 1,* , Kyoung Eun Baek 1 , Min-Ju Im 1 , Jong-Min Yoo 1 , Seung-Ho Park 1 , Ki-Jun Ryu 1 , Hyun-Tak Han 1 , Hyo-Jin Kim 1 , Soon-Chan Hong 2 , Kwang Dong Kim 1 , Yunbae Pak 1 , Jae Won Kim 1 , Chang Won Lee 1 and Jiyun Yoo 1 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 Correspondence: Jiyun Yoo, email: // Keywords : RhoGDI2, EMT, Snail, gastric cancer, invasion Received : December 23, 2013 Accepted : Febraury 5, 2014 Published : Febraury 7, 2014 Abstract 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. |
| Databáze: | OpenAIRE |
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