TY  - JOUR
A1  - Götz, Rudolf
A1  - Sendtner, Michael
T1  - Cooperation of Tyrosine Kinase Receptor TrkB and Epidermal Growth Factor Receptor Signaling Enhances Migration and Dispersal of Lung Tumor Cells
JF  - PLoS ONE
N2  - 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.
KW  - metastasis
KW  - neurons
KW  - non-small cell lung cancer
KW  - neuron migration
KW  - adenocarcinoma of the lung
KW  - vector cloning
KW  - lung and intrathoracic tumors
KW  - secondary lung tumors
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119578
SN  - 1932-6203
VL  - 9
IS  - 6
ER  - 
TY  - JOUR
A1  - Stöckli, K. A.
A1  - Lottspeich, F.
A1  - Sendtner, Michael
A1  - Masiakowski, P.
A1  - Carroll, Patrick
A1  - Götz, Rudolf
A1  - Lindholm, D.
A1  - Thoenen, Hans
T1  - Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor
N2  - CILIARY neurotrophic factor (CNTF) was originally characterized as a survival factor for chick ciliary neurons in vitro. More recently, it was shown to promote the survival of a variety of otherneuronal cell types and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of yasoactiYe intestinal peptide immunoreactiyity (VIP-IR). In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT.
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-34229
ER  -