TET2 Controls Chemoresistant Slow-cycling Cancer Cell Survival and Tumor Recurrence

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2018 Jun 27

PMID 29944140

Citations 52

Authors

Isabel Puig

Stephan P Tenbaum

Irene Chicote

Oriol Arques

Jordi Martinez-Quintanilla

Estefania Cuesta-Borras

Lorena Ramirez

Pilar Gonzalo

Atenea Soto

Susana Aguilar

Cristina Eguizabal

Ginevra Caratu

Aleix Prat

Guillem Argiles

Stefania Landolfi

Oriol Casanovas

Violeta Serra

Alberto Villanueva

Alicia G Arroyo

Luigi Terracciano

Paolo Nuciforo

Joan Seoane

Juan A Recio

Ana Vivancos

Rodrigo Dienstmann

Josep Tabernero

Hector G Palmer

Affiliations

Soon will be listed here.

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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