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World J Gastroenterol. Mar 21, 2008; 14(11): 1699-1709
Published online Mar 21, 2008. doi: 10.3748/wjg.14.1699
Activins and activin antagonists in hepatocellular carcinoma
Alev Deli, Emanuel Kreidl, Stefan Santifaller, Barbara Trotter, Katja Seir, Walter Berger, Rolf Schulte-Hermann, Chantal Rodgarkia-Dara, Michael Grusch
Alev Deli, Emanuel Kreidl, Stefan Santifaller, Barbara Trotter, Katja Seir, Walter Berger, Rolf Schulte-Hermann, Chantal Rodgarkia-Dara, Michael Grusch, Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, Vienna A-1090, Austria
Author contributions: Deli A, Kreidl E, Santifaller S, Trotter B, Seir K, and Grusch M reviewed the literature, wrote the paper, and designed the figure. Berger W, Schulte-Hermann R, and Rodgarkia-Dara C critically revised and improved the manuscript.
Correspondence to: Michael Grusch, Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, Vienna A-1090, Austria. michael.grusch@meduniwien.ac.at
Telephone: +43-1-427765144
Fax: +43-1-42779651
Received: December 4, 2007
Revised: January 1, 2008
Published online: March 21, 2008
Abstract

In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo- or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

Keywords: Hepatocellular carcinoma; Activin; Follistatin; Transforming growth factor β