RhoGDI2 Expression Is Associated with Tumor Growth and Malignant Progression of Gastric Cancer

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, angiogenesis, 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.

Rho GDP dissociation inhibitor‑β in renal cell carcinoma

“…Rho GTPases can be regulated by GDP dissociation inhibitors, including ARHGDIB (22). There is evidence that ARHGDIB is expressed differently in different tumor entities at the protein and mRNA levels; for example, ARHGDIB mRNA expression has been found to be elevated in adenocarcinoma of the ovaries (23) and shown to be positively correlated with tumor progression in gastric cancer (24). Furthermore, increased mRNA expression has been detected in breast cancer, and demonstrated to be associated with increased cell motility and invasiveness in in vitro experiments (25).…”

RhoGDI2 confers resistance to 5-fluorouracil in human gastric cancer cells

“…By contrast, another study suggested that the cleavage of RhoGDI2 by caspase-3 is not a functionally irrelevant effect of caspase activation during apoptosis but rather expedites the progression of the apoptotic process (23). Unlike bladder cancer and lymphoma cells, RhoGDI2 was reported as an oncogene in breast, colon and gastric cancer cells (9,10,24). A Korean group reported that RhoGDI2 confers resistance to cisplatin-induced apoptosis in gastric cancer cells by upregulating Bcl-2 expression and activating PLCγ (19,25).…”

“…By contrast, RhoGDI2 is overexpressed in human breast cancer cell lines and increases cancer cell invasion and motility in vitro (9). Choi et al also revealed that RhoGDI2 expression is positively correlated with tumor progression and metastasis potential in gastric cancer (10). Therefore, exploring the role of RhoGDI2 in gastric cancer is likely to aid our understanding of how it contributes to 5-FU resistance.…”

Proteomic analysis of differentially expressed serum proteins in lung cancer

“…Two-dimensional electrophoresis is a well established technique used for both qualitative and quantitative analysis of proteins, and has been applied to proteomic studies in several human cancers such as colorectal, gastric, breast, lung, prostate and pancreatic cancer [9][10][11][12][13][14]. Despite a number of limitations, the resolution of 2D gels is impressive, rendering this technology still a preferred tool in many proteomics studies [15].…”