Overexpression of Rho GDP-dissociation inhibitor alpha is associated with tumor progression and poor prognosis of colorectal cancer.

Abstract

The GDP dissociation inhibitors (GDIs) are pivotal regulators of Rho GTPases, which are essential for tumor progression, particularly in the area of metastasis. One member of GDIs was identified as RhoGDI (Rho GDP-dissociation inhibitor alpha, or RhoGDIalpha), but little is known about this protein in tumors. In this study, we used comparative proteomic analysis to show that RhoGDI is markedly up-regulated in metastatic colorectal cancer (CRC). The elevated level of RhoGDI protein in metastatic CRC was confirmed by Western blot at the tissue ( n = 24) and cell ( n = 6) levels. Further, we analyzed RhoGDI protein expression in 126 clinicopathologically characterized CRC cases by immunohistochemistry. Statistical analysis showed that there were significant differences of RhoGDI overexpression in patients categorized according to tumor invasion ( p = 0.018), lymph node metastasis ( p = 0.001) and clinical stage ( p = 0.009). A trend was also identified between high expression of RhoGDI and shorter overall survival ( p = 0.013). In the present work, we also analyzed the effect of RhoGDI on CRC cell line. Gene transfection-mediated overexpression of RhoGDI in HT29 cells, containing a low detectable level of endogenous RhoGDI, resulted in a significant increase in cell proliferation and motility in vitro. These data suggest that RhoGDI may promote CRC progression and metastasis by stimulating tumor cell growth and migration.

• Authors: Liang Zhao, Hui Wang, Jianming Li, Yawei Liu, Yanqing Ding
• Journal: Journal of proteome research (J Proteome Res) Vol. 7 Issue 9 Pg. 3994-4003 (Sep 2008) ISSN: 1535-3893 [Print] United States
• PMID: 18651761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ARHGDIA protein, human
• DNA Primers
• Guanine Nucleotide Dissociation Inhibitors
• rho Guanine Nucleotide Dissociation Inhibitor alpha
• rho-Specific Guanine Nucleotide Dissociation Inhibitors

Topics

• Base Sequence
• Blotting, Western
• Cell Line, Tumor
• Colorectal Neoplasms (metabolism, pathology)
• DNA Primers
• Disease Progression
• Electrophoresis, Gel, Two-Dimensional
• Female
• Guanine Nucleotide Dissociation Inhibitors (metabolism)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Prognosis
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Survival Analysis
• rho Guanine Nucleotide Dissociation Inhibitor alpha
• rho-Specific Guanine Nucleotide Dissociation Inhibitors