title: Activins and activin antagonists in hepatocellular carcinoma.
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 beta (TGFbeta) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo- or heterodimers formed from four different beta subunits termed betaA, betaB, betaC, and betaE, respectively. Activin A, the dimer of two betaA 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.
authors: Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, Vienna A-1090, Austria.
authors: Alev
authors: A
authors: Deli
authors: Emanuel
authors: E
authors: Kreidl
authors: Stefan
authors: S
authors: Santifaller
authors: Barbara
authors: B
authors: Trotter
authors: Katja
authors: K
authors: Seir
authors: Walter
authors: W
authors: Berger
authors: Rolf
authors: R
authors: Schulte-Hermann
authors: Chantal
authors: C
authors: Rodgarkia-Dara
authors: Michael
authors: M
authors: Grusch
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D021122:Protein Subunits; D051785:Smad Proteins; D028341:Activins; D007265:Inhibins