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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/32673

    標題: Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma
    作者: Wu, Pei-Yi
    Yu, I-Shing
    Lin, Yueh-Chien
    Chang, Yu-Tzu
    Chien-Chin Chen(陳建欽)
    Lin, Kuan-Hung
    Tseng, Tzu-Hsuan
    Kargren, Mati
    Tai, Yu-Ling
    Shen, Tang-Long
    Liu, Yen-Lin
    Wang, Bo-Jeng
    Chang, Chi-Hao
    Chen, Wei-Min
    Juan, Hsueh-Fen
    Huang, Shiu-Feng
    Chan, Ya-Yun
    Liao, Yung-Feng
    Hsu, Wen-Ming
    Lee, Hsinyu
    貢獻者: Acad Sinica, Inst Cellular & Organism Biol
    Natl Taiwan Univ, Coll Med, Lab Anim Ctr
    Natl Taiwan Univ, Dept Life Sci
    Chia Yi Christian Hosp, Dept Pathol
    Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
    Natl Taiwan Univ, Dept Plant Pathol & Microbiol
    Natl Taiwan Univ, Ctr Biotechnol
    Taipei Med Univ Hosp, Dept Pediat
    Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan
    Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan
    Natl Taiwan Univ, Coll Med
    日期: 2019-11
    上傳時間: 2020-07-29 13:54:43 (UTC+8)
    摘要: Neuroblastoma is the most common malignant disease of infancy, and amplification of the MYCN oncogene is closely associated with poor prognosis. Recently, expression of MYCN was shown to be inversely correlated with aryl hydrocarbon receptor (AHR) expression in neuroblastoma, and overexpression of AHR downregulated MYCN expression, promoting cell differentiation. Therefore, we further investigated the potential of AHR to serve as a prognostic indicator or a therapeutic target in neuroblastoma. First, the clinical significance of AHR in neuroblastoma was examined. Positive AHR immunostaining strongly correlated with differentiated histology of neuroblastoma and predicted better survival for patients. The mouse xenograft model showed that overexpression of AHR significantly suppressed neuroblastoma tumor growth. In addition, activation of AHR by the endogenous ligand kynurenine inhibited cell proliferation and promoted cell differentiation in vitro and in vivo. kynurenine treatment also upregulated the expression of KISS1, a tumor metastasis suppressor, and attenuated metastasis in the xenograft model. Finally, analysis of KISS1 levels in neuroblastoma patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for neuroblastoma, and that overexpression or activation of AHR offers a new therapeutic possibility for patients with neuroblastoma. Significance: These findings show that AHR may function as a tumor suppressor in childhood neuroblastoma, potentially influencing the aetiologic and therapeutic targeting of the disease.
    關聯: Cancer Research, v.79, n.21, pp.5550-5562
    Appears in Collections:[化妝品應用與管理系(所)] 期刊論文

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