Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 16, Pages 6524-6529Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1303932110
Keywords
bHLH; SCLC
Categories
Funding
- National Institutes of Health [R01DK55310, P50CA70907]
- Cancer Prevention and Research Institute of Texas
- Department of Defense PROSPECT
- Longenbaugh Foundation
- National Institute of General Medical Sciences Pharmacological Sciences [5-T32 GM007062]
- National Health and Medical Research Council [494511]
- Transplantation Society of Australia
- New Zealand/Allen and Hanburys Respiratory Research Fellowship
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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.
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