PMID- 24959744
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - Cooperation of tyrosine kinase receptor TrkB and epidermal growth factor receptor 
      signaling enhances migration and dispersal of lung tumor cells.
PG  - e100944
LID - 10.1371/journal.pone.0100944 [doi]
LID - e100944
AB  - TrkB mediates the effects of brain-derived neurotrophic factor (BDNF) in neuronal 
      and nonnneuronal cells. Based on recent reports that TrkB can also be 
      transactivated through epidermal growth-factor receptor (EGFR) signaling and thus 
      regulates migration of early neurons, we investigated the role of TrkB in 
      migration of lung tumor cells. Early metastasis remains a major challenge in the 
      clinical management of non-small cell lung cancer (NSCLC). TrkB receptor 
      signaling is associated with metastasis and poor patient prognosis in NSCLC. 
      Expression of this receptor in A549 cells and in another adenocarcinoma cell 
      line, NCI-H441, promoted enhanced migratory capacity in wound healing assays in 
      the presence of the TrkB ligand BDNF. Furthermore, TrkB expression in A549 cells 
      potentiated the stimulatory effect of EGF in wound healing and in Boyden chamber 
      migration experiments. Consistent with a potential loss of cell polarity upon 
      TrkB expression, cell dispersal and de-clustering was induced in A549 cells 
      independently of exogeneous BDNF. Morphological transformation involved extensive 
      cytoskeletal changes, reduced E-cadherin expression and suppression of E-cadherin 
      expression on the cell surface in TrkB expressing tumor cells. This function 
      depended on MEK and Akt kinase activity but was independent of Src. These data 
      indicate that TrkB expression in lung adenoma cells is an early step in tumor 
      cell dissemination, and thus could represent a target for therapy development.
FAU - Gotz, Rudolf
AU  - Gotz R
AD  - Institute for Clinical Neurobiology, University Hospital Wurzburg, Wurzburg, 
      Germany.
FAU - Sendtner, Michael
AU  - Sendtner M
AD  - Institute for Clinical Neurobiology, University Hospital Wurzburg, Wurzburg, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140624
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cadherins)
RN  - 0 (Membrane Glycoproteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
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)
SB  - IM
MH  - Cadherins/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/*genetics
MH  - Cell Polarity/genetics
MH  - Epidermal Growth Factor/genetics/metabolism/*physiology
MH  - Humans
MH  - Lung Neoplasms/genetics/*metabolism/pathology
MH  - Membrane Glycoproteins/genetics/metabolism/*physiology
MH  - Neoplasm Metastasis
MH  - Protein-Tyrosine Kinases/genetics/metabolism/*physiology
MH  - Receptor, trkB
MH  - Signal Transduction
PMC - PMC4069166
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/25 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/06/24
CRDT- 2014/06/25 06:00
PHST- 2014/02/25 00:00 [received]
PHST- 2014/06/01 00:00 [accepted]
PHST- 2014/06/25 06:00 [entrez]
PHST- 2014/06/25 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/06/24 00:00 [pmc-release]
AID - PONE-D-14-08696 [pii]
AID - 10.1371/journal.pone.0100944 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 24;9(6):e100944. doi: 10.1371/journal.pone.0100944. 
      eCollection 2014.