RhoGTPases and Rho-effectors in hepatocellular carcinoma metastasis: ROCK N' Rho move it

Abstract

Hepatocellular carcinoma (HCC) is an intractable disease with an extremely high mortality rate. Metastasis is the major factor of liver failure, tumour recurrence and death in HCC patients. Unfortunately, no promising curative therapy for HCC metastasis is available as yet; therefore, treatment for advanced HCC still remains a formidable challenge. A large body of evidence has demonstrated that the RhoGTPases/Rho-effector pathway plays important roles in mediating HCC metastasis based on their foremost functions in orchestrating the cell cytoskeletal reorganization. This review will first discuss the general principles of cancer metastasis and cancer cell movement with a particular focus on HCC. We will then summarize the implications of various members in the RhoGTPases/Rho-effectors signalling cascade including the upstream RhoGTPase regulators RhoGTPases and Rho-effectors and their downstream targets in HCC metastasis. Finally, we will discuss the therapeutic insight of targeting the RhoGTPases/Rho-effector pathway in HCC. Taken together, the literature demonstrates the importance of the RhoGTPases/Rho-effector signalling pathway in HCC metastasis and marks the necessity to have a more thorough knowledge of this complicated signalling network in order to develop novel therapeutic strategies for HCC patients. © 2010 John Wiley & Sons A/S.