| Literature DB >> 29944140 |
Isabel Puig1, Stephan P Tenbaum1, Irene Chicote1, Oriol Arqués1, Jordi Martínez-Quintanilla1, Estefania Cuesta-Borrás1, Lorena Ramírez2, Pilar Gonzalo3, Atenea Soto4,5, Susana Aguilar6, Cristina Eguizabal7, Ginevra Caratù8, Aleix Prat9, Guillem Argilés2, Stefania Landolfi5,10, Oriol Casanovas6, Violeta Serra11,12, Alberto Villanueva13, Alicia G Arroyo3, Luigi Terracciano14, Paolo Nuciforo15, Joan Seoane4,5,12, Juan A Recio16, Ana Vivancos8, Rodrigo Dienstmann5,17, Josep Tabernero2,12, Héctor G Palmer1,12.
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.Entities:
Keywords: Cancer; Epigenetics; Expression profiling; Oncology
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Year: 2018 PMID： 29944140 PMCID： PMC6118637 DOI： 10.1172/JCI96393
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808