title: Sonic Hedgehog pathway is essential for neuroblastoma cell proliferation and tumor growth.
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.
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, No.10, Changjiang Zhilu, Daping, Yuzhong District, Chongqing 400042, China.
authors.forename: Lunshan
authors.initials: L
authors.lastname: Xu
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wan
authors.forename: Tai
authors.initials: T
authors.lastname: Li
authors.forename: Xueyang
authors.initials: X
authors.lastname: Gong
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Yi
authors.forename: Zhonghuai
authors.initials: Z
authors.lastname: Xiang
authors.forename: Minhui
authors.initials: M
authors.lastname: Xu
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015197:Carcinogenicity Tests; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009380:Neoplasms, Nerve Tissue / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009432:Neural Crest / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human; D014704:Veratrum Alkaloids; C000541:cyclopamine