Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Ji,Jun; Feng,Xiaojing; Shi,Min; Cai,Qu; Yu,Yingyan; Zhu,Zhenggang; Zhang,Jun

doi:10.3892/ijo.2015.2836

Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Authors:
- Jun Ji
- Xiaojing Feng
- Min Shi
- Qu Cai
- Yingyan Yu
- Zhenggang Zhu
- Jun Zhang
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Affiliations: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Clinical Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: January 13, 2015 https://doi.org/10.3892/ijo.2015.2836
Pages: 1343-1353

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Abstract

Rac1 is a member of the Rho GTPase family. Rac1 activity is critical in regulating cytoskeleton organization and thus, modulates a diverse spectrum of cellular functions in normal and malignant cells. The aims of the present study were to investigate the expression pattern and clinical significance of Rac1, as well as the role of Rac1 in gastric cancer tumorigenesis and metastasis. The expression of Rac1 in human gastric cancer was explored by immunohistochemistry. The correlation of Rac1 expression with the clinicopathological characteristics and the survival of patients were analyzed by Pearson's Chi-square and Kaplan-Meier analyses, respectively. Rac1 overexpression cell model was used to examine in vitro and in vivo effects of Rac1 in cell growth, migration and invasion. Rac1 was highly expressed in gastric cancer tissues and correlated with differentiation, local invasion, lymph node metastasis and Lauren's classification. Rac1 expression in gastric cancer predicted shorter survival. Overexpression of Rac1 in gastric cancer cells dramatically induced Rac1 activation and rendered a more aggressive phenotype such as increased cell growth and migration/invasion in vitro and in vivo. Inhibiting Rac1 activity by specific inhibitor abrogated the effects of Rac1 on the malignant phenotype. Our clinical findings demonstrated that Rac1 was well correlated with aggressiveness and a negative prognostic factor. In addition, our data on experimental cell models supported the fundamental role of Rac1 in gastric cancer. Given its pivotal role in gastric tumorigenesis and progression, Rac1 can serve as a promising therapeutic target for gastric cancer.

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