Overexpression of RhoE Has a Prognostic Value in Non–Small Cell Lung Cancer
ABSTRACT Increasing evidence has suggested that RhoE plays an important role in carcinogenesis and progression. However, the correlation between RhoE expression and clinical outcome in lung cancer has not been investigated.
RhoE expression was detected by immunohistochemistry on tissue microarray containing samples from 115 patients with non-small cell lung cancer with a median follow-up of 54 months.
RhoE was overexpressed in the cytoplasm of lung cancer cells compared with undetectable expression of RhoE in the adjacent nontumoral cells. Patients with RhoE-negative tumors had substantially longer cancer-related survival than did patients with RhoE-positive tumors. Multivariate analysis showed that RhoE overexpression was an independent marker for cancer-related survival in the entire population after adjusting for other prognostic factors.
RhoE expression may serve as an unfavorable prognostic factor in patients with non-small cell lung cancer.
- SourceAvailable from: Saeid Ghavami
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- "In contrast, Rho proteins expression and/or activity are frequently altered in a variety of human cancers. For instance RhoA, RhoE, RhoC, RhoF Rac1, Rac2, Rac3, Cdc42 and Wrch2/RhoV are frequently overexpressed in many types of cancers (Faried, et al., 2005; Gomez del Pulgar, Benitah, Valeron, Espina, & Lacal, 2005; Gouw, Reading, Jenson, Lim, & Elenitoba-Johnson, 2005; Islam, et al., 2009; X. R. Li, et al., 2006; Ma, et al., 2010; Varker, Phelps, King, & Williams, 2003; C. Zhang, et al., 2007). Despite these observations, RhoA down-regulation in rare conditions such as human renal cell carcinoma has also been reported (Pu, et al., 2008). "
ABSTRACT: The cholesterol biosynthesis pathway, also known as the mevalonate (MVA) pathway, is an essential cellular pathway that is involved in diverse cell functions. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) is the rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of HMG-CoA to MVA. Given its role in cholesterol and isoprenoid biosynthesis, the regulation of HMGCR has been intensely investigated. Because all cells require a steady supply of MVA, both the sterol (i.e. cholesterol) and non-sterol (i.e. isoprenoid) products of MVA metabolism exert coordinated feedback regulation on HMGCR through different mechanisms. The proper functioning of HMGCR as the proximal enzyme in the MVA pathway is essential under both normal physiologic conditions and in many diseases given its role in cell cycle pathways and cell proliferation, cholesterol biosynthesis and metabolism, cell cytoskeletal dynamics and stability, cell membrane structure and fluidity, mitochondrial function, proliferation, and cell fate. The blockbuster statin drugs (‘statins’) directly bind to and inhibit HMGCR, and their use for the past thirty years has revolutionized the treatment of hypercholesterolemia and cardiovascular diseases, in particular coronary heart disease. Initially thought to exert their effects through cholesterol reduction, recent evidence indicates that statins also have pleiotropic immunomodulatory properties independent of cholesterol lowering. In this review we will focus on the therapeutic applications and mechanisms involved in the MVA cascade including Rho GTPase and Rho kinase (ROCK) signaling, statin inhibition of HMGCR, geranylgeranyltransferase (GGTase) inhibition, and farnesyltransferase (FTase) inhibition in cardiovascular disease, pulmonary diseases (e.g. asthma and chronic obstructive pulmonary disease (COPD), and cancer.Pharmacology [?] Therapeutics 07/2014; 143(1). DOI:10.1016/j.pharmthera.2014.02.007 · 9.72 Impact Factor
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ABSTRACT: Rho GTPases are small proteins that act as binary molecular switches in a wide range of signalling pathways upon stimulation of cell surface receptors. Three different classes of regulatory proteins control their activity. In the activated state small GTPases are able to bind a variety of effector proteins and initiate downstream signalling. Rho GTPases regulate important cellular processes ranging from cytoskeletal remodelling and gene expression to cell proliferation and membrane trafficking. Therefore it is not surprising that deregulated Rho signalling can contribute to disturbed cellular phenotypes in a wide range of diseases. The main focus of this review will be the diversity of functions of Rho GTPases and the effects of aberrant Rho GTPase signalling in various aspects of cancer.Clinical and Experimental Metastasis 02/2007; 24(8):657-72. DOI:10.1007/s10585-007-9119-1 · 3.49 Impact Factor
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ABSTRACT: Rho GTPases are major regulators of signal transduction pathways and play key roles in processes including actin dynamics, cell cycle progression, cell survival and gene expression, whose deregulation may lead to tumorigenesis. A growing number of in vitro and in vivo studies using tumor-derived cell lines, primary tumors and animal cancer models strongly suggest that altered Rho GTPase signaling plays an important role in the initiation as well as in the progression of hepatocellular carcinoma (HCC), one of the deadliest human cancers in the world. These alterations can occur at the level of the GTPases themselves or of one of their regulators or effectors. The participation into the tumorigenic process can occur either through the over-expression of one of these components which presents an oncogenic activity as illustrated with RhoA and C or through the attenuation of the expression of a component presenting tumor suppressor activity as for Cdc42 or the RhoGAP, DLC-1. Consequently, these observations reflect the heterogeneity and the complexity of liver carcinogenesis. Recently, pharmacological approaches targeting Rho GTPase signaling have been used in HCC-derived models with relative success but remain to be validated in more physiologically relevant systems. Therefore, therapeutic approaches targeting Rho GTPase signaling may provide a novel alternative for anti-HCC therapy.Biochimica et Biophysica Acta 02/2009; 1795(2):137-51. DOI:10.1016/j.bbcan.2008.12.003 · 4.66 Impact Factor