Role of TET1 and 5hmC in an Obesity-Linked Pathway Driving Cancer Stem Cells in Triple-Negative Breast Cancer.
Mol Cancer Res
; 18(12): 1803-1814, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32913111
ABSTRACT
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks expression of estrogen receptor, progesterone receptor, and the HER2 but is enriched with cancer stem cell-like cells (CSC). CSCs are the fraction of cancer cells recognized as the source of primary malignant tumors that also give rise to metastatic recurrence. 5-Hydroxymethylcytosine (5hmC) is a DNA epigenetic feature derived from 5-methylcytosine by action of tet methylcytosine dioxygenase enzymes (e.g., TET1); and although TET1 and 5hmC are required to maintain embryonic stem cells, the mechanism and role in CSCs remain unknown. Data presented in this report support the conclusion that TET1 and TET1-dependent 5hmC mediate hydrogen peroxide (H2O2)-dependent activation of a novel gene expression cascade driving self-renewal and expansion of CSCs in TNBC. Evidence presented also supports that the H2O2 affecting this pathway arises due to endogenous mechanisms-including downregulation of antioxidant enzyme catalase in TNBC cells-and by exogenous routes, such as systemic inflammation and oxidative stress coupled with obesity, a known risk factor for TNBC incidence and recurrence. IMPLICATIONS This study elucidates a pathway dependent on H2O2 and linked to obesity-driven TNBC tumor-initiating CSCs; thus, it provides new understanding that may advance TNBC prevention and treatment strategies.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Proteínas Proto-Oncogênicas
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5-Metilcitosina
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Proteínas de Ligação a DNA
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Neoplasias de Mama Triplo Negativas
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Fatores de Processamento de Serina-Arginina
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Oxigenases de Função Mista
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Obesidade
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Cancer Res
Assunto da revista:
BIOLOGIA MOLECULAR
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NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article