TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence.
J Clin Invest
; 128(9): 3887-3905, 2018 08 31.
Article
em En
| MEDLINE
| ID: mdl-29944140
ABSTRACT
Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir responsible for relapse in patients, years after curative surgery and adjuvant therapy. We have adapted the pulse-chase expression of H2BeGFP for labeling and isolating slow-cycling cancer cells (SCCCs). SCCCs showed cancer initiation potential and enhanced chemoresistance. Cells at this slow-cycling status presented a distinctive nongenetic and cell-autonomous gene expression profile shared across different tumor types. We identified TET2 epigenetic enzyme as a key factor controlling SCCC numbers, survival, and tumor recurrence. 5-Hydroxymethylcytosine (5hmC), generated by TET2 enzymatic activity, labeled the SCCC genome in carcinomas and was a predictive biomarker of relapse and survival in cancer patients. We have shown the enhanced chemoresistance of SCCCs and revealed 5hmC as a biomarker for their clinical identification and TET2 as a potential drug target for SCCC elimination that could extend patients' survival.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Proteínas de Ligação a DNA
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Neoplasias
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article