PMID- 23936232
OWN - NLM
STAT- MEDLINE
DCOM- 20140401
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Upregulation of TrkB promotes epithelial-mesenchymal transition and anoikis 
      resistance in endometrial carcinoma.
PG  - e70616
LID - 10.1371/journal.pone.0070616 [doi]
LID - e70616
AB  - Mechanisms governing the metastasis of endometrial carcinoma (EC) are poorly 
      defined. Recent data support a role for the cell surface receptor tyrosine kinase 
      TrkB in the progression of several human tumors. Here we present evidence for a 
      direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB 
      and its secreted ligand, brain-derived neurotrophic factor (BDNF), are more 
      highly expressed in EC than in normal endometrium. High TrkB levels correlated 
      with lymph node metastasis (p<0.05) and lymphovascular space involvement (p<0.05) 
      in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the 
      migratory and invasive capacity of cancer cell lines in vitro and resulted in 
      anoikis in suspended cells. Conversely, exogenous expression of TrkB increased 
      cell migration and invasion and promoted anoikis resistance in suspension 
      culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in 
      altered the expression of molecular mediators of the epithelial-to-mesenchymal 
      transition (EMT). RNA interference (RNAi)-mediated depletion of the downstream 
      regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in 
      vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC 
      cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial 
      transition and anoikis in vivo. Our data support a novel function for TrkB in 
      promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential 
      therapeutic target in human EC.
FAU - Bao, Wei
AU  - Bao W
AD  - Department of Obstetrics and Gynecology, International Peace Maternity and Child 
      Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Qiu, Haifeng
AU  - Qiu H
FAU - Yang, Tingting
AU  - Yang T
FAU - Luo, Xin
AU  - Luo X
FAU - Zhang, Huijuan
AU  - Zhang H
FAU - Wan, Xiaoping
AU  - Wan X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130730
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Twist-Related Protein 1)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Anoikis/*genetics
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics/metabolism
MH  - Endometrial Neoplasms/*genetics/pathology
MH  - Enzyme Activation/drug effects
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Receptor, trkB/antagonists & inhibitors/*genetics/metabolism
MH  - Tumor Burden
MH  - Tumor Cells, Cultured
MH  - Twist-Related Protein 1/metabolism
PMC - PMC3728299
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/13 06:00
MHDA- 2014/04/02 06:00
PMCR- 2013/07/30
CRDT- 2013/08/13 06:00
PHST- 2013/02/27 00:00 [received]
PHST- 2013/06/19 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/04/02 06:00 [medline]
PHST- 2013/07/30 00:00 [pmc-release]
AID - PONE-D-13-08953 [pii]
AID - 10.1371/journal.pone.0070616 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 30;8(7):e70616. doi: 10.1371/journal.pone.0070616. Print 2013.