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 t...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 factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA 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 coreceptors 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.展开更多
文摘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 factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA 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 coreceptors 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.
