Abstract
Accumulated evidence suggests a major role for the activation of the Sonic Hedgehog (SHH) signaling pathway in the development of neural crest stem cells that give rise to the sympathetic nervous system. We therefore investigated the involvement of SHH signaling in the pathogenesis of neuroblastoma (NB), a common childhood malignant tumor of the sympathetic nervous system. Inhibition of SHH signaling by cyclopamine induced apoptosis and blocked proliferation in all major types of NB cells, and abrogated the tumorigenicity of NB cells. Our study has revealed a molecular mechanism for the persistent activation of the SHH pathway which promotes the development of NB, and suggests a new approach for the treatment of this childhood malignant tumor.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis / drug effects
-
Carcinogenicity Tests
-
Cell Cycle / drug effects
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Gene Expression Regulation, Neoplastic
-
Hedgehog Proteins / antagonists & inhibitors
-
Hedgehog Proteins / genetics
-
Hedgehog Proteins / metabolism*
-
Humans
-
Molecular Targeted Therapy
-
Neoplasms, Nerve Tissue / metabolism*
-
Neoplasms, Nerve Tissue / pathology
-
Neoplastic Stem Cells / metabolism
-
Neoplastic Stem Cells / pathology
-
Neural Crest / metabolism
-
Neural Crest / pathology
-
Neuroblastoma / metabolism*
-
Neuroblastoma / pathology
-
Signal Transduction*
-
Sympathetic Nervous System / metabolism
-
Sympathetic Nervous System / pathology
-
Veratrum Alkaloids / pharmacology
Substances
-
Hedgehog Proteins
-
SHH protein, human
-
Veratrum Alkaloids
-
cyclopamine