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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Stem+Cells 2014 ; 32 (9): 2309-23 Nephropedia Template TP
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Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1 #MMPMID24809620
Choi DS; Blanco E; Kim YS; Rodriguez AA; Zhao H; Huang THM; Chen CL; Jin G; Landis MD; Burey LA; Qian W; Granados SM; Dave B; Wong HH; Ferrari M; Wong ST; Chang JC
Stem Cells 2014[Sep]; 32 (9): 2309-23 PMID24809620show ga
Triple negative breast cancer (TNBC) is known to contain a high percentage of CD44+/CD24?/low cancer stem cells (CSC), corresponding with a poor prognosis despite systemic chemotherapy. Chloroquine (CQ), an anti-malarial drug, is a lysotropic reagent which inhibits autophagy. CQ was identified as a potential CSC inhibitor through in silico gene expression signature analysis of the CD44+/CD24?/low CSC population. Autophagy plays a critical role in adaptation to stress conditions in cancer cells, and is related with drug resistance and CSC maintenance. Thus the objectives of this study were to examine the potential enhanced efficacy arising from addition of chloroquine (CQ) to standard chemotherapy (paclitaxel) in TNBC and to identify the mechanism by which CQ eliminates CSCs in TNBCs. Herein, we report that CQ sensitizes TNBC cells to paclitaxel through inhibition of autophagy and reduces the CD44+/CD24?/low CSC population in both preclinical and clinical settings. Also, we are the first to report a mechanism by which CQ regulates the CSCs in TNBC through inhibition of the Janus-activated kinase 2 (Jak2) - Signal transducer and activator of transcription 3 (STAT3) signaling pathway by reducing the expression of Jak2 and DNA methyltransferase 1 (DNMT1).