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International Journal of Hepatology
Volume 2012, Article ID 958673, 8 pages
Review Article

Watch the GAP: Emerging Roles for IQ Motif-Containing GTPase-Activating Proteins IQGAPs in Hepatocellular Carcinoma

1Department of Medicine, Stony Brook University, Stony Brook, NY 11794-8151, USA
2Division of Hematology, Stony Brook University, HSC T15-053, Stony Brook, NY 11794-8151, USA

Received 11 May 2012; Revised 25 July 2012; Accepted 3 August 2012

Academic Editor: Weiliang Xia

Copyright © 2012 Valentina A. Schmidt. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


IQ motif-containing GTPase-activating proteins IQGAP1 and IQGAP2 are highly homologous multidomain scaffolding proteins. Their major function consists of integration of Rho GTPase and Ca2+/calmodulin signals with cell adhesive and cytoskeletal reorganizational events. Recent studies showed that they play an important role in carcinogenesis. There is growing evidence that IQGAP2 is a novel tumor suppressor counteracting the effects of IQGAP1, an oncogene, in several cancers, especially in hepatocellular carcinoma (HCC). While HCC is highly prevalent and one of the deadliest cancers worldwide, the signaling pathways involved are not fully understood and treatment of advanced disease still represents an area of high unmet medical need. This paper compiles various findings from studies in mouse models, cell lines, and patient samples that support future development of IQGAPs into new therapeutic targets. It also discusses distinct features of IQGAP2 in an attempt to provide insight into the mechanism of the seemingly paradoxical opposing roles of the two very similar IQGAP proteins in carcinogenesis.