UNIGE document Scientific Article
previous document  unige:101822  next document
add to browser collection

Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma

Crippa, Stefania
Ancey, Pierre-Benoit
Vazquez, Jessica
Angelino, Paolo
Guettier, Catherine
Zoete, Vincent
Delorenzi, Mauro
show hidden authors show all authors [1 - 10]
Published in EMBO Molecular Medicine. 2017, vol. 9, no. 11, p. 1589-1604
Abstract Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent CTNNB1 mutations, hepatoblastoma is a Wnt/β-catenin-driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma. First, we demonstrated that glucose transporter GLUT3 is a direct TCF4/β-catenin target gene. RNA sequencing enabled to identify molecular and metabolic features specific to hepatoblastoma and revealed that several glycolytic enzymes are overexpressed in embryonal-like compared to fetal-like tumor cells. This led us to implement successfully three biomarkers to distinguish embryonal from fetal components by immunohistochemistry from a large panel of human hepatoblastoma samples. Functional analyses demonstrated that embryonal-like hepatoblastoma cells are highly glycolytic and sensitive to hexokinase-1 silencing. Altogether, our findings reveal a new, metabolic classification of human hepatoblastoma, with potential future implications for patients' diagnosis and treatment.
PMID: 28923827
Full text
Article (Published version) (2.8 MB) - public document Free access
(ISO format)
CRIPPA, Stefania et al. Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma. In: EMBO Molecular Medicine, 2017, vol. 9, n° 11, p. 1589-1604. https://archive-ouverte.unige.ch/unige:101822

86 hits



Deposited on : 2018-01-31

Export document
Format :
Citation style :