[Frontiers in Bioscience 16, 2561-2571, June 1, 2011]

[Frontiers in Bioscience 16, 2561-2571, June 1, 2011]

Role of Rho GTPases and their regulators in cancer progression

Rajamani Rathinam¹, Allison Berrier², Suresh K. Alahari¹

1Department of Biochemistry and Molecular Biology, Stanley Scott Cancer Center, ²Department of Oral Biology, LSU Health Science Center, New Orleans, LA 70112

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Regulation of Rho, Rac and CDC42 in cancer: 3.1. Rac1 in cancer; 3.2. RhoA in cancer; 3.3. CDC42 in cancer
4. Guanine nucleotide exchange factors (GEFs): 4.1. Rac1 GEFs in cancer; 4.2. RhoA GEF in cancer; 4.3. CDC42 GEF in cancer; 4.4. Other regulators of Rho GTPases
5. RHO GTPase mediated signaling pathways: 5.1. Rac signaling; 5.2. CDC42 Signaling; 5.3. RhoA signaling; 5.4. Integrins and Rho GTPase signaling
6. Perspective
7. References

1. ABSTRACT

Rho family of GTPases is an ubiquitiously expressed and evolutionarily conserved family of GTP binding proteins that regulate actin dynamics and intracellular signaling. Among the Rho family GTPases, three members RhoA, Rac1 and CDC42 have been well characterized. They each play pivotal roles in gene expression, cell proliferation, apoptosis and various cellular functions. They are driven by signaling from RhoGDIs, RhoGEFs, RhoGAPs and cell surface receptors. Abnormalities in Rho GTPase function have major consequences on cell behavior. Over expression of Rho GTPases is associated with reorganization of actin cytoskeleton, an increase in cell migration, invasion and metastasis which are important aspects of cancer progression. This review will explore these Rho GTPases and the function of their associated signaling pathways in different types of cancers.