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RhoC is essential for the metastasis of gastric cancer

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Abstract

Rho family members are known to regulate malignant transformation and motility of cancer cells, but the clinicopathological significance of RhoC remains unclear yet in the case of gastric cancer. In this study, we evaluated the protein expression level of RhoC in gastric cancer tissues and cell lines. Results showed that only weak staining of RhoC was detected in 3 of 33 non-tumorous cases by immunohistochemistry. The expression of RhoC was significantly higher in gastric cancer tissues (23/42, 54.8%) than in non-tumorous tissues (p < 0.01). Further analysis demonstrated that RhoC had high specificity (80.0%) in detecting gastric carcinomas with metastatic potential. RhoC was positively expressed in 18 out of 20 metastases (90.0%), even higher than that in primary gastric cancer tissues. Western blot showed that RhoC was up-regulated in five different gastric cancer cell lines but not expressed in SV40-transformed immortal gastric epithelial cell GES-1. Overexpression of RhoC GTPase in GES-1 cells could produce the motile and invasive phenotype but did not alter the monolayer growth rate. To further study the functions of RhoC, we took the powerful siRNA technology to knock down the expression of RhoC in SGC7901 cells. It was shown that down-regulation of RhoC did not affect the proliferation of SGC7901 cells. However, interference of RhoC expression could inhibit migration, invasion, and anchorage-independent growth of SGC7901 cells. In conclusion, RhoC may play a very important role in the metastasis of gastric carcinoma. Therapeutic strategies targeting RhoC and RhoC-mediated pathways may be a novel approach for treating metastasis of gastric cancer.

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Abbreviations

SiRNA:

small interfering RNA

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Acknowledgements

We thank technicians Taidong Qiao and Zheng Chen for their excellent technical assistance. This work was supported by the National Outstanding Youth Foundation (Grant 30325039) and the National Natural Science Foundation of China (Grant 30400535).

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Authors and Affiliations

  1. State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi Province, People’s Republic of China

    Na Liu, Guoyun Zhang, Feng Bi, Yanglin Pan, Yan Xue, Yongquan Shi, Liping Yao, Lina Zhao & Daiming Fan

  2. Division of Experimental Hematology, Children’s Hospital Research Foundation, University of Cincinnati, Cincinnati, OH, USA

    Yi Zheng

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  1. Na Liu
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  2. Guoyun Zhang
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  3. Feng Bi
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  5. Yan Xue
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  6. Yongquan Shi
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Correspondence to Feng Bi or Daiming Fan.

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N. Liu and G. Zhang contributed equally to this work.

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Liu, N., Zhang, G., Bi, F. et al. RhoC is essential for the metastasis of gastric cancer. J Mol Med 85, 1149–1156 (2007). https://doi.org/10.1007/s00109-007-0217-y

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  • DOI: https://doi.org/10.1007/s00109-007-0217-y

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