RhoC is essential for the metastasis of gastric cancer
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.
KeywordsRho GTPase Gastric cancer Metastasis siRNA
small interfering RNA
- 4.Sahai E, Marshall CJ (2002) Rho-GTPases and cancer. Nat Rev 2:133–142Google Scholar
- 23.van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, Chandrasekharappa S, Strawderman M, Ethier SP, Merajver SD (1999) A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res 5(9):2511–2519PubMedGoogle Scholar
- 26.Faried A, Faried LS, Kimura H, Nakajima M, Sohda M, Miyazaki T, Kato H, Usman N, Kuwano H (2006) RhoA and RhoC proteins promote both cell proliferation and cell invasion of human oesophageal squamous cell carcinoma cell lines in vitro and in vivo. Eur J Cancer 42(10):1455–1465PubMedCrossRefGoogle Scholar
- 32.Pille JY, Denoyelle C, Varet J, Bertrand JR, Soria J, Opolon P, Lu H, Pritchard LL, Vannier JP, Malvy C, Soria C, Li H (2005) Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo. Mol Ther 11(2):267–274PubMedCrossRefGoogle Scholar