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Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival
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Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival
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Journal Article
Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival
2021
Overview
Purpose
Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic factor and potential therapeutic target in adult hepatocellular carcinoma, we investigated the expression of its gene
ASNS
and of the gene
GLUL,
encoding for glutamine synthetase, in hepatoblastoma specimens and cell lines and investigated the correlation with overall survival.
Methods
We correlated
GLUL
and
ASNS
expression with overall survival using publicly available microarray and clinical data. We examined
GLUL
and
ASNS
expression by RT-qPCR and by Western blot analysis in the embryonal cell lines Huh-6 and HepT1, and in five hepatoblastoma specimens. In the same cell lines, we investigated the effects of glutamine depletion. Hepatoblastoma biopsies were examined for histology and
CTNNB1
mutations.
Results
High
GLUL
expression was associated with a higher median survival time. Independent of mutations and histology, hepatoblastoma samples showed strong
GLUL
expression and glutamine synthesis. Glutamine depletion resulted in the inhibition of proliferation and of cell viability in both embryonal hepatoblastoma cell lines.
ASNS
expression did not correlate with overall survival.
Conclusion
Growth inhibition resulting from glutamine depletion, as described for the hepatoblastoma fetal subtype, is also detected in established embryonal hepatoblastoma cell lines carrying different mutations. At variance with adult hepatocellular carcinoma, in hepatoblastoma asparagine synthetase has no prognostic significance.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Biopsy
/ Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor - biosynthesis
/ Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor - genetics
/ Exons
/ Fetuses
/ Glutamate-Ammonia Ligase - biosynthesis
/ Glutamate-Ammonia Ligase - genetics
/ Humans
/ Liver Neoplasms - metabolism
/ Medicine
/ Mutation
/ Oncology
/ Original Article – Cancer Research
/ Tumors
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