NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas

Jihan K. Osborne, Marcy L. Guerra, Joshua X. Gonzales, Elizabeth A. McMillan, John D. Minna, Melanie H. Cobb

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Cigarette smoking is a major risk factor for acquisition of small cell lung cancer (SCLC). A role has been demonstrated for the basic helix-loop-helix transcription factor NeuroD1 in the pathogenesis of neural and neuroendocrine lung cancer, including SCLC. In the present study we investigate the possible function of NeuroD1 in established tumors, as well as actions early on in pathogenesis, in response to nicotine. We demonstrate that nicotine up-regulates NeuroD1 in immortalized normal bronchial epithelial cells and a subset of undifferentiated carcinomas. Increased expression of NeuroD1 subsequently leads to regulation of expression and function of the nicotinic acetylcholine receptor subunit cluster of α3, α5, and β4. In addition, we find that coordinated expression of these subunits by NeuroD1 leads to enhanced nicotine-induced migration and invasion, likely through changes in intracellular calcium. These findings suggest that aspects of the pathogenesis of neural and neuroendocrine lung cancers may be affected by a nicotine- and NeuroD1-induced positive feedback loop.

Original languageEnglish (US)
Pages (from-to)1782-1792
Number of pages11
JournalMolecular Biology of the Cell
Volume25
Issue number11
DOIs
StatePublished - Jun 1 2014

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Neuroendocrine Carcinoma
Nicotinic Receptors
Nicotine
Small Cell Lung Carcinoma
Lung Neoplasms
Basic Helix-Loop-Helix Transcription Factors
Up-Regulation
Smoking
Epithelial Cells
Calcium
Carcinoma
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas. / Osborne, Jihan K.; Guerra, Marcy L.; Gonzales, Joshua X.; McMillan, Elizabeth A.; Minna, John D.; Cobb, Melanie H.

In: Molecular Biology of the Cell, Vol. 25, No. 11, 01.06.2014, p. 1782-1792.

Research output: Contribution to journalArticle

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