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© Research
Publication : Cancer cell

Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer

Team: Archived: Group: Yu Wei
Team: Archived: Pathogenesis of Hepatitis B Virus
Team: Group: Humanized mice for infectious disease modeling
Team: Innate Immunity
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cancer cell - 01 Dec 2008

Cairo S, Armengol C, De Reyniès A, Wei Y, Thomas E, Renard CA, Goga A, Balakrishnan A, Semeraro M, Gresh L, Pontoglio M, Strick-Marchand H, Levillayer F, Nouet Y, Rickman D, Gauthier F, Branchereau S, Brugières L, Laithier V, Bouvier R, Boman F, Basso G, Michiels JF, Hofman P, Arbez-Gindre F, Jouan H, Rousselet-Chapeau MC, Berrebi D, Marcellin L, Plenat F, Zachar D, Joubert M, Selves J, Pasquier D, Bioulac-Sage P, Grotzer M, Childs M, Fabre M, Buendia MA

Link to Pubmed [PMID] – 19061838

Cancer Cell 2008 Dec;14(6):471-84

Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy.