0000000000134741

AUTHOR

Marcus Buschbeck

showing 3 related works from this author

Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma.

2017

Hepatocellular carcinomas (HCC) contain a subpopulation of cancer stem cells (CSCs), which exhibit stem cell–like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem-cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic-cell reprogramming. Here, we focused on the role played by the histone variant macroH2A1 as a potential epigenetic factor promoting CSC differentiation. In human HCC section…

0301 basic medicineCarcinoma HepatocellularBiologyMetastasisHistones03 medical and health sciencesCancer stem cellHistone H2AmedicineHumansEpigeneticsPhosphorylationCell ProliferationHepatologyCell growthGene Expression ProfilingLiver NeoplasmsTranscription Factor RelAHep G2 Cellsmedicine.disease030104 developmental biologyHistoneCancer cellCancer researchbiology.proteinNeoplastic Stem CellsReprogrammingHepatology (Baltimore, Md.)
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DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…

2016

Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…

0301 basic medicineEpigenomicsCHROMATINCancer ResearchLIVERCancer Research; OncologyGene ExpressionSECRETORY PHENOTYPEHCV CORE PROTEINHistonesCell MovementProtein IsoformsCellular SenescenceEpigenomicsAged 80 and overMice KnockoutbiologyLiver NeoplasmsMETHYLATIONHep G2 CellsCANCERChromatinHistoneOncologyDNA methylationAzacitidineDisease ProgressionCell agingSTEM-CELLSSenescenceAdultEXPRESSIONCarcinoma HepatocellularArticle5-AZA-2'-DEOXYCYTIDINE03 medical and health sciencesCell Line TumorAnimalsHumansEpigeneticsCell ProliferationDNA Methylationbeta-GalactosidaseMolecular biologyMice Inbred C57BLMICE030104 developmental biologybiology.proteinCancer researchDNA hypomethylation
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Histone Variant MacroH2A1 Marks Liver Aging and Orchestrates the Escape from Senescence Induced by DNA Hypomethylation in Hepatocellular Carcinoma

2015

The epigenetic basis of age-associated progression of liver diseases towards hepatocellular carcinoma (HCC) is unclear. MacroH2A1 is a variant of histone H2A1, present in the two isoforms, with fundamental roles in cell homeostasis. MacroH2A1 is a marker of senescence associated heterochromatic foci (SAHF) and synergizes with DNA demethylating chemotherapic agent 5-aza-2'-deoxycytidine (5-aza-dC) in silencing tumor suppressor genes in human fibroblasts. We show that protein levels of macroH2A1 isoforms are increased in the livers of old rodents and humans, and in human HCC tissue. Human HCC cells overexpressing macroH2A1 escape a 5-aza-dC-induced senescent phenotype, as determined by cell p…

SenescencebiologyCell growthCell cycleBiochemistryCell biologyHistoneGeneticsbiology.proteinGene silencingEpigeneticsMolecular BiologyGeneBiotechnologyDNA hypomethylation
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