PMID- 24531713
OWN - NLM
STAT- MEDLINE
DCOM- 20150410
LR  - 20211203
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 34
IP  - 6
DP  - 2015 Feb 5
TI  - The TrkB+ cancer stem cells contribute to post-chemotherapy recurrence of 
      triple-negative breast cancers in an orthotopic mouse model.
PG  - 761-70
LID - 10.1038/onc.2014.8 [doi]
AB  - Cancer stem cells (CSCs) are believed to have a crucial role in triple-negative 
      breast cancer (TNBC) recurrence. However, the exact mechanisms that are 
      functionally critical in CSCs-mediated recurrence remain unclear. Here, we showed 
      that CSCs derived from recurrent TNBCs are endowed with increased self-renewal 
      capacity as compared with those from the matched primary lesions. Using 
      patient-derived specimens, we demonstrated the existence of paracrine 
      brain-derived neurotrophic factor (BDNF) signaling between differentiated 
      recurrent TNBC cells and CSCs characterized by the expression of TrkB, the 
      receptor of BDNF. We showed that paclitaxel induced BDNF expression and apoptosis 
      simultaneously in a cell cycle-dependent manner. BDNF promotes the self-renewal 
      potential of the TrkB+CSCs through induction of KLF4. The TrkB+CSCs represent a 
      particular subset indispensable for TNBC relapse. In line with this, TrkB is 
      proved to be a superior predictor for TNBC recurrence. Using a genetically 
      engineered mouse model of TNBC, we observed that ablation of the TrkB+CSCs 
      potentially prevents relapse of malignant tumors. Further preclinical 
      investigation of this promising approach may lead to development of a novel 
      therapeutic strategy to improve the devastating prognosis of TNBC patients.
FAU - Yin, B
AU  - Yin B
AD  - Department of Radiology, HuaShan Hospital, Fudan University, Shanghai, P.R. 
      China.
FAU - Ma, Z Y
AU  - Ma ZY
AD  - Department of General Surgery, HuaShan Hospital, Fudan University, Shanghai, P.R. 
      China.
FAU - Zhou, Z W
AU  - Zhou ZW
AD  - Department of Pathology, HuaShan Hospital, Fudan University, Shanghai, P.R. 
      China.
FAU - Gao, W C
AU  - Gao WC
AD  - Department of General Surgery, ChangZheng Hospital, the Second Military Medical 
      University, Shanghai, P.R. China.
FAU - Du, Z G
AU  - Du ZG
AD  - Department of Pathology, HuaShan Hospital, Fudan University, Shanghai, P.R. 
      China.
FAU - Zhao, Z H
AU  - Zhao ZH
AD  - Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, 
      P.R. China.
FAU - Li, Q Q
AU  - Li QQ
AD  - Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, 
      P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140217
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (KLF4 protein, human)
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Membrane Glycoproteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Apoptosis/genetics
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Kruppel-Like Factor 4
MH  - Membrane Glycoproteins/*biosynthesis/genetics
MH  - Mice
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/chemically induced/*genetics/pathology
MH  - Neoplastic Stem Cells/*drug effects
MH  - Paclitaxel/administration & dosage
MH  - Paracrine Communication/drug effects
MH  - Protein-Tyrosine Kinases/*biosynthesis/genetics
MH  - Receptor, trkB
MH  - Signal Transduction
MH  - Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology
EDAT- 2014/02/18 06:00
MHDA- 2015/04/11 06:00
CRDT- 2014/02/18 06:00
PHST- 2013/09/16 00:00 [received]
PHST- 2013/12/17 00:00 [revised]
PHST- 2014/01/06 00:00 [accepted]
PHST- 2014/02/18 06:00 [entrez]
PHST- 2014/02/18 06:00 [pubmed]
PHST- 2015/04/11 06:00 [medline]
AID - onc20148 [pii]
AID - 10.1038/onc.2014.8 [doi]
PST - ppublish
SO  - Oncogene. 2015 Feb 5;34(6):761-70. doi: 10.1038/onc.2014.8. Epub 2014 Feb 17.