Proteomics-based Strategy to Delineate the Molecular Mechanisms of RhoGDI2-induced Metastasis and Drug Resistance in Gastric Cancer

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• 作者：Hee Jun Cho ; Kyoung Eun Baek ; In-Kyu Kim ; Sun-Mi Park ; Yeong-Lim Choi ; In-Koo Nam ; Seung-Ho Park ; Min-Ju Im ; Jong-Min Yoo ; Ki-Jun Ryu ; Young Taek Oh ; Soon-Chan Hong ; Oh-Hyung Kwon ; Jae Won Kim ; Chang Won Lee ; Jiyun Yoo
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：April 6, 2012
• 年：2012
• 卷：11
• 期：4
• 页码：2355-2364
• 全文大小：468K
• 年卷期：v.11,no.4(April 6, 2012)
• ISSN：1535-3907

文摘

Rho GDP dissociation inhibitor 2 (RhoGDI2) was initially identified as a regulator of the Rho family of GTPases. Our recent works suggest that RhoGDI2 promotes tumor growth and malignant progression, as well as enhances chemoresistance in gastric cancer. Here, we delineate the mechanism by which RhoGDI2 promotes gastric cancer cell invasion and chemoresistance using two-dimensional gel electrophoresis (2-DE) on proteins derived from a RhoGDI2-overexpressing SNU-484 human gastric cancer cell line and control cells. Differentially expressed proteins were identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). In total, 47 differential protein spots were identified; 33 were upregulated, and 14 were downregulated by RhoGDI2 overexpression. Upregulation of SAE1, Cathepsin D, Cofilin1, CIAPIN1, and PAK2 proteins was validated by Western blot analysis. Loss-of-function analysis using small interference RNA (siRNA) directed against candidate genes reveals the need for CIAPIN1 and PAK2 in RhoGDI2-induced cancer cell invasion and Cathepsin D and PAK2 in RhoGDI2-mediated chemoresistance in gastric cancer cells. These data extend our understanding of the genes that act downstream of RhoGDI2 during the progression of gastric cancer and the acquisition of chemoresistance.

Keywords:

RhoGDI2; gastric cancer; metastasis; invasion; cisplatin resistance; CIAPIN1; PAK2; cathepsin D