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Cooperation of Tyrosine Kinase Receptor TrkB and Epidermal Growth Factor Receptor Signaling Enhances Migration and Dispersal of Lung Tumor Cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-119578
  • 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. ExpressionTrkB 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.show moreshow less

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Metadaten
Author: Rudolf Götz, Michael Sendtner
URN:urn:nbn:de:bvb:20-opus-119578
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Neurobiologie
Language:English
Parent Title (English):PLoS ONE
ISSN:1932-6203
Year of Completion:2014
Volume:9
Issue:6
Pagenumber:e100944
Source:PLOS ONE 9(6): e100944. doi:10.1371/journal.pone.0100944
DOI:https://doi.org/10.1371/journal.pone.0100944
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24959744
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 571 Physiologie und verwandte Themen
Tag:adenocarcinoma of the lung; lung and intrathoracic tumors; metastasis; neuron migration; neurons; non-small cell lung cancer; secondary lung tumors; vector cloning
Release Date:2015/11/09
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung