Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma

doi:10.1158/0008-5472.CAN-18-3272

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Title:	Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma
Authors:	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
Contributors:	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
Keywords:	BREAST-CANCER CELLS AH RECEPTOR KISS-1 EXPRESSION GENE-EXPRESSION N-MYC PROTEIN PROLIFERATION IDENTIFICATION INDUCTION MELANOMA
Date:	2019-11
Issue Date:	2020-07-29 13:54:43 (UTC+8)
Publisher:	AMER ASSOC CANCER RESEARCH
Abstract:	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.
Relation:	Cancer Research, v.79, n.21, pp.5550-5562
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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