Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells

Epigenetics : Official Journal of the DNA Methylation Society
Oriana Lo ReManlio Vinciguerra

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 pathwa...Continue Reading

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Citations

May 18, 2019·Cancers·Sebastiano GiallongoManlio Vinciguerra
Nov 14, 2019·Cancers·Gianluigi MazzoccoliAntonio Grieco
Oct 28, 2019·Stem Cells·Malini VisweswaranArun Dharmarajan
Jun 23, 2020·Antioxidants & Redox Signaling·Sebastiano GiallongoManlio Vinciguerra
Jul 17, 2020·British Journal of Pharmacology·Lorenzo Pontini, Maura Marinozzi
Apr 18, 2019·Biotechnology Letters·Ke-Tao JinXiao-Zhou Mou
Aug 21, 2020·Clinical Epigenetics·Diana BuzovaManlio Vinciguerra
Nov 18, 2018·Cancers·Hayato NakagawaKazuhiko Koike
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Juan Li, Ying Zhu
Feb 12, 2021·Nature Reviews. Cancer·Flávia G GhiraldiniEmily Bernstein
Mar 9, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Jan FrohlichManlio Vinciguerra
Apr 10, 2021·Expert Review of Anticancer Therapy·Homa Fatma, Hifzur Rahman Siddique
Nov 14, 2020·International Journal of Molecular Sciences·Irma Magaly Rivas SernaManlio Vinciguerra
Jun 3, 2021·Cancers·Filippo PelizzaroFabio Farinati
Jul 31, 2021·Journal of Experimental & Clinical Cancer Research : CR·Daniel Otero-Albiol, Amancio Carnero

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Datasets Mentioned

BETA
GSE117459

Methods Mentioned

BETA
RNA-Seq
fluorescence microscopy
xenograft
transfection
PCR
ELISA

Software Mentioned

R
edgeR R package
R package mixOmics
R Development Core Team
Ingenuity Pathway Analysis ( IPA )
STAR
Ingenuity Pathway Analysis

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