期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 128, 期 9, 页码 3887-3905出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI96393
关键词
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资金
- Fundacion Cientifica de la Asociacion Espanola Contra el Cancer
- Fundacion Olga Torres and Red Tematica de Investigacion Cooperativa en Cancer [RD12/0036/0012]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca
- Ministerio de Economia y Competitividad [SAF2014-52050-R]
- Instituto de Salud Carlos III through 4 consecutive grants [PI08/1356, PI11/02499, PI14/00103, PI17/00945]
- CIBERONC Network
- TRANSCAN-TACTIC [AC15/00064]
- Miguel Servet contract [MSII14/00037]
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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