ArticleEpigenetics2018
Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells.
Article in Epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Comparative analysis of metabolome and transcriptomes to explore the inhibited influence of sonodynamic therapy combined with lonidamine on hepatocellular carcinoma.Drug delivery · 2025Article
- Histone-based liquid biopsy discriminates between myelodysplastic syndrome and solid malignancies.Clinical epigenetics · 2025Article
- Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.International journal of cancer · 2025Review
- Lipid Metabolism Reprogramming in Tumor-Associated Macrophages Modulates Their Function in Primary Liver Cancers.Cancers · 2025Review
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.Molecular diagnosis & therapy · 2025Article
- Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation.Frontiers in immunology · 2025Review
- Cancer stem cells: advances in the glucose, lipid and amino acid metabolism.Molecular and cellular biochemistry · 2024Review
- Deficiency of histone variant macroH2A1.1 is associated with sexually dimorphic obesity in mice.Scientific reports · 2023Article
- Detection of cell-free histones in the cerebrospinal fluid of pediatric central nervous system malignancies by imaging flow cytometry.Frontiers in molecular biosciences · 2023Article
- Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study.Hepatology communications · 2022Article
- Abnormal lipid synthesis as a therapeutic target for cancer stem cells.World journal of stem cells · 2022Review
- The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance.Cell death & disease · 2021Review
- The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma.Biomedicines · 2021Article
- Cellular senescence or stemness: hypoxia flips the coin.Journal of experimental & clinical cancer research : CR · 2021Review
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- Review
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- Solid tumours hijack the histone variant network.Nature reviews. Cancer · 2021Review
- Histone-fold centromere protein W (CENP-W) is associated with the biological behavior of hepatocellular carcinoma cells.Bioengineered · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinomas (HCCs) contain a sub-population of cancer stem cells (CSCs) that are responsible for tumor relapse, metastasis, and chemoresistance. We recently showed that loss of macroH2A1, a variant of the histone H2A and an epigenetic regulator of stem-cell function, in HCC leads to CSC-like features such as resistance to chemotherapeutic agents and growth of large and relatively undifferentiated tumors in xenograft models. These HCC cells silenced for macroH2A1 also exhibited stem-like metabolic changes consistent with enhanced glycolysis. However, there is no consensus as to the metabolic characteristics of CSCs that render them adaptable to microenvironmental changes by conveniently shifting energy production source or by acquiring intermediate metabolic phenotypes. Here, we assessed long-term proliferation, energy metabolism, and central carbon metabolism in human hepatoma HepG2 cells depleted in macroH2A1. MacroH2A1-depleted HepG2 cells were insensitive to serum exhaustion and showed two distinct, but interdependent changes in glucose and lipid metabolism in CSCs: (1) massive upregulation of acetyl-coA that is transformed into enhanced lipid content and (2) increased activation of the pentose phosphate pathway, diverting glycolytic intermediates to provide precursors for nucleotide synthesis. Integration of metabolomic analyses with RNA-Seq data revealed a critical role for the Liver X Receptor pathway, whose inhibition resulted in attenuated CSCs-like features. These findings shed light on the metabolic phenotype of epigenetically modified CSC-like hepatic cells, and highlight a potential approach for selective therapeutic targeting.
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