Intracellular signaling and hepatocellular carcinoma.
Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underlying liver cancer progression. Although these studies identified gene expression signatures in hepatocellular carcinoma, the early steps of the development of hepatocellular carcinomas (HCC) are not well understood. The development of HCC is a multistep process which includes the progressive alterations of gene expression leading to the increased proliferation and to liver cancer. This review summarizes recent progress in the identification of the key steps of the development of HCC with the focus on early events of carcinogenesis and on the role of translational and epigenetic alterations in the development of HCC. Quiescent stage of the liver is supported by several tumor suppressor proteins including p53, Rb and C/EBPα. Studies with chemical models of liver carcinogenesis and with human HCC have shown that the elevation of gankyrin is responsible for the elimination of these three proteins at early steps of carcinogenesis. Later stages of progression of the liver cancer are associated with alterations in many signaling pathways including translation which leads to epigenetic silencing/activation of many genes. Particularly, recent reports suggest a critical role of histone deacetylase 1, HDAC1, in the development of HCC through the interactions with transcription factors such as C/EBP family proteins.
Iakova
Polina
P
Department of Pathology and Immunology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States.
Timchenko
Lubov
L
Timchenko
Nikolai A
NA
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C496283:Fxr1h protein, mouse; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D046988:Proteasome Endopeptidase Complex