Activins and activin antagonists in hepatocellular carcinoma - PubMed (original) (raw)

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Activins and activin antagonists in hepatocellular carcinoma

Alev Deli et al. World J Gastroenterol. 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 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.

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Figure 1

Figure 1

Graphic representation of activin signaling and interaction points with activin antagonists. A: Activin dimers first bind the type II activin receptors, which then recruit and phosphorylate typeIreceptors. These in turn phosphorylate receptor-activated Smads, which subsequently form a complex with Smad 4 and are translocated to the nucleus, where they regulate the transcription of target genes; B: Activin antagonists can block activin signals by: (1) Binding activins in the extracellular space like follistatin or FLRG and thereby blocking their access to activin receptors; (2) Acting as inhibitory co-receptors, which prevent ligand receptor interactions (Cripto) or receptor dimerization (BAMBI); (3) Competing with receptor-activated Smads 2 and 3 for binding sites on activin receptors (Smad 7).

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References

    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. - PubMed
    1. Chen JG, Zhu J, Parkin DM, Zhang YH, Lu JH, Zhu YR, Chen TY. Trends in the incidence of cancer in Qidong, China, 1978-2002. Int J Cancer. 2006;119:1447–1454. - PubMed
    1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576. - PubMed
    1. Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology. 2002;122:1609–1619. - PubMed
    1. Chung DC. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. Gastroenterology. 2000;119:854–865. - PubMed

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