PUBLICATION
Phospholipid isotope tracing suggests β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma
- Authors
- VanSant-Webb, C., Low, H.K., Kuramoto, J., Stanley, C.E., Qiang, H., Su, A., Ross, A.N., Cooper, C.G., Cox, J.E., Summers, S.A., Evason, K.J., Ducker, G.S.
- ID
- ZDB-PUB-240527-3
- Date
- 2024
- Source
- Biochimica et biophysica acta. Molecular and cell biology of lipids 1869(6): 159514 (Journal)
- Registered Authors
- Evason, Kimberley, VanSant-Webb, Chad
- Keywords
- Ceramides, Hepatocellular carcinoma, Isotope tracing, Lipid metabolism, Phospholipids, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Carcinoma, Hepatocellular*/genetics
- Carcinoma, Hepatocellular*/metabolism
- Carcinoma, Hepatocellular*/pathology
- Cell Line, Tumor
- Humans
- Lipid Metabolism/genetics
- Lipidomics/methods
- Liver Neoplasms*/genetics
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Phosphatidylcholines*/metabolism
- Phospholipids/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- beta Catenin*/genetics
- beta Catenin*/metabolism
- PubMed
- 38795827 Full text @ BBA Molecular and Cell Biology of Lipids
Citation
VanSant-Webb, C., Low, H.K., Kuramoto, J., Stanley, C.E., Qiang, H., Su, A., Ross, A.N., Cooper, C.G., Cox, J.E., Summers, S.A., Evason, K.J., Ducker, G.S. (2024) Phospholipid isotope tracing suggests β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma. Biochimica et biophysica acta. Molecular and cell biology of lipids. 1869(6):159514.
Abstract
Activating mutations in the CTNNB1 gene encoding β-catenin are among the most frequently observed oncogenic alterations in hepatocellular carcinoma (HCC). Profound alterations in lipid metabolism, including increases in fatty acid oxidation and transformation of the phospholipidome, occur in HCC with CTNNB1 mutations, but it is unclear what mechanisms give rise to these changes. We employed untargeted lipidomics and targeted isotope tracing to measure phospholipid synthesis activity in an inducible human liver cell line expressing mutant β-catenin, as well as in transgenic zebrafish with activated β-catenin-driven HCC. In both models, activated β-catenin expression was associated with large changes in the lipidome including conserved increases in acylcarnitines and ceramides and decreases in triglycerides. Lipid isotope tracing analysis in human cells revealed a reduction in phosphatidylcholine (PC) production rates as assayed by choline incorporation. We developed lipid isotope tracing analysis for zebrafish tumors and observed reductions in phosphatidylcholine synthesis by both the CDP-choline and PEMT pathways. The observed changes in the β-catenin-driven HCC phospholipidome suggest that zebrafish can recapitulate conserved features of HCC lipid metabolism and may serve as a model for identifying future HCC-specific lipid metabolic targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping