NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM

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 neu...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (16), p.6524-6529
Main Authors: Osborne, Jihan K., Larsen, Jill E., Shields, Misty D., Gonzales, Joshua X., Shames, David S., Sato, Mitsuo, Kulkarni, Ashwinikumar, Wistuba, Ignacio I., Girard, Luc, Minna, John D., Cobb, Melanie H.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biological Sciences
Carbazoles
Cell adhesion & migration
Cell Line, Tumor
Cell lines
Cell Movement - physiology
Cell Survival - physiology
Chromatin Immunoprecipitation
DNA Primers - genetics
Epithelial cells
Humans
Immunoblotting
Immunoprecipitation
Kinases
Luciferases
Lung cancer
Lung neoplasms
Lung Neoplasms - metabolism
Lung Neoplasms - physiopathology
Lungs
Metastasis
Mice
Microarray Analysis
Neural cell adhesion molecules
Neural Cell Adhesion Molecules - metabolism
Neuroendocrine carcinoma
Neurons
Plasmids - genetics
Real-Time Polymerase Chain Reaction
Receptor, trkB - metabolism
Signal transduction
Small Cell Lung Carcinoma - metabolism
Small Cell Lung Carcinoma - physiopathology
Tumor cell line
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 tropomyosinrelated 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1303932110