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Sonic Hedgehog pathway is essential for neuroblastoma cell proliferation and tumor growth

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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.

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Abbreviations

SHH:

Sonic Hedgehog

NB:

Neuroblastoma

FBS:

Fetal bovine serum

Toma:

Tomatidine

Cyclo:

Cyclopamine

BrdU:

5-Bromo-2_-deoxyuridine

PFA:

Paraformaldehyde

PI:

Propidium iodide

7-AAD:

7-Aminoactinomycin D

PBS:

Phosphate-buffered saline

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Acknowledgments

The authors are grateful for Dr. Han-fei Ding and Dr. Qingyou Xia for their invaluable support. This study were supported by the National Basic Research Program of China (No. 2012cb114603), the National Natural Science Foundation of China (No. 31172268, 30872649/C1608, 81172413), and the Natural Science Foundation Project of CQ (No. cstc 2011jjA8007).

Conflicts of interest

The authors are not employed by any commercial companies that may influence during the performance of this study

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Authors and Affiliations

  1. Department of Urology, Center of Nephropathy, Second Affiliated Hospital, Third Military Medical University, Chongqing, China

    Xiangwei Wang

  2. Department of Neurosurgery, Daping Hospital, Third Military Medical University, No.10, Changjiang Zhilu, Daping, Yuzhong District, Chongqing, 400042, China

    Lunshan Xu, Liang Yi & Minhui Xu

  3. State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, 216 Tiansheng Road, Beibei District, Chongqing, 400716, China

    Jianhua Wan, Tai Li, Xueyang Gong, Kui Zhang, Zhonghuai Xiang & Hongjuan Cui

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  1. Lunshan Xu
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  2. Xiangwei Wang
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  3. Jianhua Wan
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  4. Tai Li
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  5. Xueyang Gong
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  6. Kui Zhang
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  7. Liang Yi
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  8. Zhonghuai Xiang
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  9. Minhui Xu
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  10. Hongjuan Cui
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Corresponding authors

Correspondence to Minhui Xu or Hongjuan Cui.

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Xu, L., Wang, X., Wan, J. et al. Sonic Hedgehog pathway is essential for neuroblastoma cell proliferation and tumor growth. Mol Cell Biochem 364, 235–241 (2012). https://doi.org/10.1007/s11010-011-1222-6

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  • DOI: https://doi.org/10.1007/s11010-011-1222-6

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