RhoGDI2 expression is associated with tumor growth and malignant progression of gastric cancer

Hee Jun Cho, Kyoung Eun Baek, Sun Mi Park, In Kyu Kim, Yeong Lim Choi, Hye Jung Cho, In Koo Nam, Eun Mi Hwang, Jae Yong Park, Jae Yoon Han, Sang Soo Kang, Dong Chul Kim, Won Sup Lee, Mi Ni Lee, Gootaeg Oh, Jae Won Kim, Chang Won Lee, Jiyun Yoo

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Purpose: Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of Rho family GTPase. However, there is currently no direct evidence suggesting whether RhoGDI2 activates or inhibits Rho family GTPase in vivo (and which type), and the role of RhoGDI2 in tumor remains controversial. Here, we assessed the effects of RhoGDI2 expression on gastric tumor growth and metastasis progression. Experimental Design: Proteomic analysis was done to investigate the tumor-specific protein expression in gastric cancer and RhoGDI2 was selected for further study. Immunohistochemistry was used to detect RhoGDI2 expression in clinical samples of primary gastric tumor tissues which have different pathologic stages. Gain-of-function and loss-of-function approaches were done to examine the malignant phenotypes of the RhoGDI2-expressing or RhoGDI2-depleting cells. Results: RhoGDI2 expression was correlated positively with tumor progression and metastasis potential in human gastric tumor tissues, as well as cell lines. The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogen- esis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects. Conclusion: Our findings indicate that RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer.

Original languageEnglish
Pages (from-to)2612-2619
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number8
DOIs
StatePublished - 15 Apr 2009

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