C/EBPα‐dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer

• DOI: 10.1002/hep.29677
• Publication Date: 2017-11-21T09:37:39Z
• Authors: Ashley Cast; Leila Valanejad; Mary Wright; Phuong Nguyen; Anita Gupta; Liqin Zhu; Soona Shin; Nikolai Timchenko
• Keywords: Hepatoblastoma; Liver Cancer; Liver tumor

Recent publications show that classic hepatoblastoma (HBL) is the result of failure hepatic stem cells to differentiate into hepatocytes, while hepatocellular carcinoma (HCC) caused by dedifferentiation hepatocytes cancer cells. However, mechanisms aggressive HBL and cause are unknown. We found that, similar HCC but opposite HBL, In both cases liver cancer, dephosphorylation tumor suppressor protein CCAAT/enhancer binding α (C/EBPα) at Ser193 (Ser190 in human protein) or mutation Ala results a modified with oncogenic activities. have investigated mouse model C/EBPα‐S193A, large cohort samples, Pten/p53 double knockout mice these cancers characterized elevation C/EBPα dephosphorylated Ser190/193. creates preneoplastic foci give rise HBL. C/EBPα‐dependent includes increased proliferation followed generation multinucleated subsequent appearance delta‐like 1 homolog–positive intranuclear inclusions. further isolated they possess characteristics tumor‐initiating cells, including cell markers. observed patients predisposition for cancer. Conclusion: The earliest steps adult pediatric identical features include conversion an isoform, which where dedifferentiate giving (H epatology 2018;67:1857‐1871).