title: NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM.
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 NeuroD1. TrkB and NCAM may be therapeutic targets for aggressive neuroendocrine cancers that express NeuroD1.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
authors.forename: Jihan K
authors.initials: JK
authors.lastname: Osborne
authors.forename: Jill E
authors.initials: JE
authors.lastname: Larsen
authors.forename: Misty D
authors.initials: MD
authors.lastname: Shields
authors.forename: Joshua X
authors.initials: JX
authors.lastname: Gonzales
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sato
authors.forename: Ashwinikumar
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002227:Carbazoles; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005663:Furans; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases; D008175:Lung Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D046228:Microarray Analysis; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002227:Carbazoles; D017931:DNA Primers; D005663:Furans; D008156:Luciferases; D019006:Neural Cell Adhesion Molecules; D020813:Receptor, trkB; C093970:NEUROD1 protein, human; C119379:lestaurtinib
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