NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition

J. K. Osborne, J. E. Larsen, J. X. Gonzales, D. S. Shames, M. Sato, I. I. Wistuba, L. Girard, J. D. Minna, M. H. Cobb

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pigmented melanoma but not in prostate cell lines. We also found that loss of the tumor suppressor p53 increased NeuroD1 expression in normal human bronchial epithelial cells and cancer cells with neuroendocrine features. Although we found that a major mechanism of action of NeuroD1 is by the regulation of TrkB, effective targeting of TrkB to inhibit invasion may depend on the cell of origin. These findings suggest that NeuroD1 is a lineage-dependent oncogene acting through its downstream target, TrkB, across multiple cancer types, which may provide new insights into the pathogenesis of neuroendocrine cancers.

Original languageEnglish (US)
Article numbere63
JournalOncogenesis
Volume2
DOIs
StatePublished - 2013

Fingerprint

Neuroendocrine Carcinoma
Prostate
Melanoma
Neoplasms
Neural Cell Adhesion Molecules
Cell Line
Neuroendocrine Cells
Neuroendocrine Tumors
Oncogenes
Transcription Factors
Epithelial Cells
Lung

Keywords

  • migration
  • NeuroD1
  • neuroendocrine
  • TrkB

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition. / Osborne, J. K.; Larsen, J. E.; Gonzales, J. X.; Shames, D. S.; Sato, M.; Wistuba, I. I.; Girard, L.; Minna, J. D.; Cobb, M. H.

In: Oncogenesis, Vol. 2, e63, 2013.

Research output: Contribution to journalArticle

Osborne, J. K. ; Larsen, J. E. ; Gonzales, J. X. ; Shames, D. S. ; Sato, M. ; Wistuba, I. I. ; Girard, L. ; Minna, J. D. ; Cobb, M. H. / NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition. In: Oncogenesis. 2013 ; Vol. 2.
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