Table of Contents
Molecular Biology International
Volume 2012, Article ID 849874, 8 pages
Review Article

Pathogenetic and Prognostic Significance of Inactivation of RASSF Proteins in Human Hepatocellular Carcinoma

Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany

Received 29 November 2011; Accepted 26 January 2012

Academic Editor: Dae-Sik Lim

Copyright © 2012 Diego F. Calvisi et al. 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.


Hepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide, with limited treatment options and a dismal prognosis. Thus, there is a strong need to expand the basic and translational research on this deadly disease in order to improve the prognosis of HCC patients. Although the etiologic factors responsible for HCC development have been identified, the molecular pathogenesis of liver cancer remains poorly understood. Recent evidence has shown the frequent downregulation of Ras association domain family (RASSF) proteins both in the early and late stages of hepatocarcinogenesis. Here, we summarize the data available on the pathogenetic role of inactivation of RASSF proteins in liver cancer, the molecular mechanisms responsible for suppression of RASSF proteins in HCC, and the possible clinical implications arising from these discoveries. Altogether, the data indicate that inactivation of the RASSF1A tumor suppressor is ubiquitous in human liver cancer, while downregulation of RASSF2 and RASSF5 proteins is limited to specific HCC subsets. Also, the present findings speak in favour of therapeutic strategies aimed at reexpressing RASSF1A, RASSF2, and RASSF5 genes and/or inactivating the RASSF cellular inhibitors for the treatment of human liver cancer.