Abstract
Small-cell lung cancer and other aggressive neuroendocrine cancers are often associated with early dissemination and frequent metastases. We demonstrate that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. We find that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosin-related kinase B (TrkB). Like TrkB, the prometastatic signaling molecule neural cell adhesion molecule (NCAM) is a downstream target of NeuroD1, whose impaired expression mirrors loss of NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Carbazoles
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Cell Line, Tumor
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Cell Movement / physiology*
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Cell Survival / physiology*
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Chromatin Immunoprecipitation
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DNA Primers / genetics
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Furans
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Humans
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Immunoblotting
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Immunoprecipitation
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Luciferases
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Lung Neoplasms / metabolism
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Lung Neoplasms / physiopathology*
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Mice
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Microarray Analysis
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Neural Cell Adhesion Molecules / metabolism*
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Plasmids / genetics
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Real-Time Polymerase Chain Reaction
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Receptor, trkB / metabolism*
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Small Cell Lung Carcinoma / metabolism
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Small Cell Lung Carcinoma / physiopathology*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Carbazoles
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DNA Primers
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Furans
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NEUROD1 protein, human
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Neural Cell Adhesion Molecules
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lestaurtinib
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Luciferases
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Receptor, trkB