Rho GTPases: potential candidates for anticancer therapy

Abstract 

Low molecular weight Rho GTPases are proteins that, in response to diverse stimuli, control key cellular processes such as cell proliferation, apoptosis, lipid metabolism, cytoarchitecture, adhesion, migration, cell polarity, and transcriptional regulation. The high incidence of overexpression of some members of the Rho family of GTPases in human tumors suggests that these proteins are important in the carcinogenic process, and therefore potential candidates for a therapeutic intervention. In recent years, the characterization of downstream effectors to Rho GTPases has increased our understanding of the general cellular effects that permit aberrant proliferation and motility of tumor cells. In addition, several transcription factors have been identified to play important roles at various levels of Rho-induced tumorigenesis. Accordingly, drugs that specifically alter Rho signaling display antineoplastic properties both at the level of tumor growth and tumor metastasis. In this review, a brief summary of the progress made in understanding the biological functions elicited by Rho GTPases that contribute to tumor biology will be made. In addition, a description of new drugs available targeted to specific elements of Rho signaling with antineoplastic or antimetastatic activity is included.

Keywords: Rho GTPases, Human carcinogenesis, Rho effectors, Wiskott–Aldrich syndrome protein family, IQGAP, p21-Activated kinase, ROCK, Transcriptional regulation, Apoptosis, Anticancer drugs