| Author | Lo Re, Oriana | pt_BR |
| Author | Fusilli, Caterina | pt_BR |
| Author | Rappa, Francesca | pt_BR |
| Author | Van Haele, Matthias | pt_BR |
| Author | Douet, Julien | pt_BR |
| Author | Pindjakova, Jana | pt_BR |
| Author | Rocha, Sura Wanessa | pt_BR |
| Author | Pata, Illar | pt_BR |
| Author | Valčíková, Barbora | pt_BR |
| Author | Uldrijan, Stjepan | pt_BR |
| Author | Yeung, Raymond S. | pt_BR |
| Author | Peixoto, Christina Alves | pt_BR |
| Author | Roskams, Tania | pt_BR |
| Author | Buschbeck, Marcus | pt_BR |
| Author | Mazza, Tommaso | pt_BR |
| Author | Vinciguerra, Manlio | pt_BR |
| Access date | 2019-11-21T14:03:30Z | |
| Available date | 2019-11-21T14:03:30Z | |
| Document date | 2018 | |
| Citation | LO RE, Oriana et al. Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma. Hepatology, v. 67, n. 2, p. 636-650, Feb. 2018. | pt_BR |
| ISSN | 0270-9139 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/37227 | |
| Language | eng | pt_BR |
| Publisher | Wiley | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma | en_US |
| Type | Article | |
| DOI | 10.1002/hep.29519 | pt_BR |
| Abstract | 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 sections we uncovered a significant correlation between low frequencies of macroH2A1 staining and advanced, aggressive HCC subtypes with poorly differentiated tumor phenotypes. Using HCC cell lines, we found that short hairpin RNA-mediated macroH2A1 knockdown induces acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolysis. The loss of macroH2A1 increased expression of a panel of stemness-associated genes and drove hyperactivation of the nuclear factor kappa B p65 pathway. Blocking phosphorylation of nuclear factor kappa B p65 on Ser536 inhibited the emergence of CSC-like features in HCC cells knocked down for macroH2A1. Conclusion: The absence of histone variant macroH2A1 confers a CSC-like phenotype to HCC cells in vitro and in vivo that depends on Ser536 phosphorylation of nuclear factor kappa B p65; this pathway may hold valuable targets for the development of CSC-focused treatments for HCC. (Hepatology 2018;67:636-650). | en |
| Affilliation | St. Anne's University Hospital. Center for Translational Medicine. International Clinical Research Center. Brno, Czech Republic / Masaryk University. Faculty of Medicine. Department of Biology. Brno, Czech Republic. | pt_BR |
| Affilliation | IRCCS Casa Sollievo della Sofferenza. UO of Bioinformatics. San Giovanni Rotondo, Italy. | pt_BR |
| Affilliation | University of Palermo. Department of Experimental Biomedicine and Clinical Neurosciences. Palermo, Italy. | pt_BR |
| Affilliation | Katholieke Universiteit Leuven. Translational Cell & Tissue Research Unit, Department of Imaging & Pathology. Leuven, Belgium. | pt_BR |
| Affilliation | Josep Carreras Institute for Leukaemia Research. Campus ICO-GTP. Campus Can Ruti. Badalona, Spain / Germans Trias i Pujol Research Institute. Program for Predictive and Personalized Medicine of Cancer. Campus Can Ruti. Badalona, Spain. | pt_BR |
| Affilliation | St. Anne's University Hospital. Center for Translational Medicine. International Clinical Research Center. Brno, Czech Republic. | pt_BR |
| Affilliation | Faculdade de Ciências Humanas de Olinda. Olinda, PE, Brasil. | pt_BR |
| Affilliation | IVEX Lab. Tallinn, Estonia. | pt_BR |
| Affilliation | Masaryk University. Faculty of Medicine. Department of Biology. Brno, Czech Republic. | pt_BR |
| Affilliation | Masaryk University. Faculty of Medicine. Department of Biology. Brno, Czech Republic / St. Anne's University Hospital. Center of Biomolecular and Cellular Engineering. International Clinical Research Center. Brno, Czech Republic. | pt_BR |
| Affilliation | University of Washington. Northwest Liver Research Program. Department of Surgery. Seattle, WA, United States. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Ultraestrutura. Recife, PE, Brasil. | pt_BR |
| Affilliation | Katholieke Universiteit Leuven. Translational Cell & Tissue Research Unit, Department of Imaging & Pathology. Leuven, Belgium. | pt_BR |
| Affilliation | Josep Carreras Institute for Leukaemia Research. Campus ICO-GTP. Campus Can Ruti. Badalona, Spain / Germans Trias i Pujol Research Institute. Program for Predictive and Personalized Medicine of Cancer. Campus Can Ruti. Badalona, Spain. | pt_BR |
| Affilliation | IRCCS Casa Sollievo della Sofferenza. UO of Bioinformatics. San Giovanni Rotondo, Italy. | pt_BR |
| Affilliation | St. Anne's University Hospital. Center for Translational Medicine. International Clinical Research Center. Brno, Czech Republic / University College London. Institute for Liver and Digestive Health. Royal Free Hospital. London, UK. | pt_BR |
| Subject | Cancer cell stemness | en |
| Subject | Macrohistone H2A1 | en |
| Subject | Hepatocellular carcinoma | en |
| DeCS | Carcinoma Hepatocelular / patologia | pt_BR |
| DeCS | Proliferação de Células | pt_BR |
| DeCS | Perfilação da Expressão Gênica | pt_BR |
| DeCS | Células Hep G2 | pt_BR |
| DeCS | Histonas / fisiologia | pt_BR |
| DeCS | Humanos | pt_BR |
| DeCS | Neoplasias Hepáticas / patologia | pt_BR |
| DeCS | Células-Tronco Neoplásicas / patologia | pt_BR |
| DeCS | Fosforilação | pt_BR |
| DeCS | Fator de Transcrição RelA / metabolismo | pt_BR |
| e-ISSN | 1527-3350 | |
| Embargo date | 2050-01-01 | |
