[Frontiers in Bioscience 16, 1915-1926, January 1, 2011]

RhoA can lead the way in tumor cell invasion and metastasis

Amanda P. Struckhoff1, Manish K. Rana1, Rebecca A. Worthylake1

1Departments of Oral Biology and Pharmacology, LSU Health Sciences Center, New Orleans, LA 70119

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Rho expression in metastasis
3.1. RhoC expression is positively correlated with metastasis
3.2. MicroRNAs regulate tumor metastasis by modulating Rho expression
4. The RhoA pathway at the leading edge
4.1. Spatiotemporal activation measured with biosensors
4.2. Upstream activators at the leading edge
4.3. RhoA GTPase effectors at the leading edge
4.4. Formins as RhoA effectors
4.5. ROCKs as RhoA effectors
5. Invasive behaviors regulated by the RhoA pathway
5.1. RhoA GTPase pathway promotes invadopodia
5.2. RhoA GTPase pathway promotes amoeboid-like motility
5.3. RhoA pathway in plasticity of invasive behaviors
6. Perspective
7. Acknowledgements
8. References

1. ABSTRACT

The Rho family of GTPases is well-established regulators of cell migration, and has been implicated in the process of tumor cell invasion and metastasis. The RhoA signaling pathway is strongly correlated with the ability of tumor cells to invade and successfully establish metastases. In this review, we begin by discussing the gene expression data correlating Rho expression with metastasis, and then discuss two emerging concepts that help explain the underlying mechanisms by which RhoA may promote tumor metastasis. First, the use of sophisticated biosensor probes has revealed that RhoA is active in membrane protrusions. Second, the RhoA pathway affects the invasive behavior of tumor cells by promoting invadopodia, amoeboid migration, and the plasticity of tumor cells to modulate their migratory properties. Thus, our view of the role of the RhoA pathway in metastasis is evolving to include a previously unappreciated function at the leading edge.