1. TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence
- Author
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Puig, Isabel, Tenbaum, Stephan P., Chicote, Irene, Arques, Oriol, Martinez- Quintanilla, Jordi, Cuesta-Borras, Estefania, Ramirez, Lorena, Gonzalo, Pilar, Soto, Atenea, Aguilar, Susana, Eguizabal, Cristina, Caratu, Ginevra, Prat, Aleix, Argiles, Guillem, Landolfi, Stefania, Casanovas, Oriol, Serra, Violeta, Villanueva, Alberto, Arroyo, Alicia G., Terracciano, Luigi, Nuciforo, Paolo, Seoane, Joan, Recio, Juan A., Vivancos, Ana, Dienstmann, Rodrigo, Tabernero, Josep, and Palmer, Hector G.
- Subjects
Cancer treatment -- Research ,Oncogenes -- Health aspects ,Chemotherapy -- Patient outcomes ,Cancer research ,Drug resistance -- Genetic aspects ,Health care industry - 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., Introduction Cancer remains a deadly disease since patients often relapse after surgery and adjuvant therapy, progressing to advanced metastatic stages (1). Recent studies have shown that cancer cells, beyond their [...]
- Published
- 2018
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