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

Jihan K. Osborne, Jill E. Larsen, Misty D. Shields, Joshua X. Gonzales, David S. Shames, Mitsuo Sato, Ashwinikumar Kulkarni, Ignacio I. Wistuba, Luc Girard, John D. Minna, Melanie H. Cobb

Research output: Contribution to journalArticle

40 Scopus citations

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 Neu-roD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.

Original languageEnglish (US)
Pages (from-to)6524-6529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number16
DOIs
StatePublished - Apr 16 2013

ASJC Scopus subject areas

  • General

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