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**26** 

**Rho GTPases and** 

Xuejing Zhang and Daotai Nie

*Department of Medical Microbiology, Immunology, and Cell Biology* 

The Rho GTPases is a subfamily of molecular switches that cycle between an inactive GDP-bound state and an active GTP-bound state within the Ras superfamily. In the past, members of the Rho subfamily were mainly thought to be involved in the regulation of cytoskeletal organization in response to extracellular growth factors. However, a number of studies over the past few years have revealed that the Rho GTPases play crucial roles in a wide spectrum of cellular functions related to cell adhesion to the extracellular matrix, cell morphology, cell cycle progression, malignant transformation, invasion and metastasis. Alterations of the expression levels to Rho GTPases have been detected in many types of human tumors and, in some cases, up-regulation and/or overexpression of Rho protein correlates with poor prognosis. This article reviews the evidence of aberrant Rho signaling and the cellular effects elicited by Rho GTPases signaling in human breast

Rho GTPases belong to the Ras superfamily of low molecular mass (~21 kDa) proteins that are widely expressed in mammalian cells (DerMardirossian and Bokoch 2001). In mammals, the Rho family of GTPases contains 22 members which can be classified into six groups: Rho (RhoA, RhoB, RhoC), Rac (Rac1, Rac2, Rac3, RhoG), Cdc42 (Cdc42, TC10, TCL, Chp, Wrch-1), Rnd (Rnd1, Rnd2, Rnd3/RhoE), RhoBTB (RhoBTB1, RhoBTB2) and Miro (Miro-1, Miro-2) (Wennerberg and Der 2004). RhoD, Rif and RhoH/TTF have not been grouped yet. RhoA, Rac1 and Cdc42 are the best-characterized family members of Rho family GTPases. Each controls the formation of a distinct cytoskeletal element in mammalian cells. Activation of Rac induces Actin polymerization to form lamellipodia (Ridley, Paterson et al. 1992), whereas activation of CDC42 stimulates the polymerization of actin to filopodia or microspikes (Nobes and Hall 1995). In contrast, Rho regulates bundling of actin filaments into stress fibers and the formation of focal adhesion complexes (Keely, Westwick et al.

**1. Introduction** 

tumors.

1997).

**2. Categorization** 

*University School of Medicine and Simmons Cancer Institute* 

**Breast Cancer** 

*Southern Illinois* 

*Springfield USA* 

osteoclastogenesis. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 21(9):2025-34.

