https://scholars.lib.ntu.edu.tw/handle/123456789/582946
標題: | Quantitative Proteomics of Th-MYCN Transgenic Mice Reveals Aurora Kinase Inhibitor Altered Metabolic Pathways and Enhanced ACADM to Suppress Neuroblastoma Progression | 作者: | Hsieh, Chiao-Hui Cheung, Chantal Hoi Yin Liu, Yen-Lin Hou, Chun-Li CHIA-LANG HSU Huang, Chen-Tsung Yang, Tsai-Shan Chen, Sung-Fang CHIUNG-NIEN CHEN WEN-MING HSU Huang, Hsuan-Cheng Juan, Hsueh-Fen |
關鍵字: | aurora kinases;metabolic pathway;MYCN;neuroblastoma;quantitative proteomics;tozasertib;transgenic mice | 公開日期: | 2019 | 出版社: | American Chemical Society | 卷: | 18 | 期: | 11 | 起(迄)頁: | 3850-3866 | 來源出版物: | Journal of Proteome Research | 摘要: | Neuroblastoma is a neural crest-derived embryonal tumor and accounts for about 15% of all cancer deaths in children. MYCN amplification is associated with aggressive and advanced stage of high-risk neuroblastoma, which remains difficult to treat and exhibits poor survival under current multimodality treatment. Here, we analyzed the transcriptomic profiles of neuroblastoma patients and showed that aurora kinases lead to poor survival and had positive correlation with MYCN amplification and high-risk disease. Further, pan-aurora kinase inhibitor (tozasertib) treatment not only induces cell-cycle arrest and suppresses cell proliferation, migration, and invasion ability in MYCN-amplified (MNA) neuroblastoma cell lines, but also inhibits tumor growth and prolongs animal survival in Th-MYCN transgenic mice. Moreover, we performed quantitative proteomics and identified 150 differentially expressed proteins after tozasertib treatment in the Th-MYCN mouse model. The functional and network-based enrichment revealed that tozasertib alters metabolic processes and identified a mitochondrial flavoenzyme in fatty acid β-oxidation, ACADM, which is correlated with aurora kinases and neuroblastoma patient survival. Our findings indicate that the aurora kinase inhibitor could cause metabolic imbalance, possibly by disturbing carbohydrate and fatty acid metabolic pathways, and ACADM may be a potential target in MNA neuroblastoma. © 2019 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073263358&doi=10.1021%2facs.jproteome.9b00245&partnerID=40&md5=083e7790fbdd6e3e03cd2e5f9030a8e1 https://scholars.lib.ntu.edu.tw/handle/123456789/582946 |
ISSN: | 1535-3893 | DOI: | 10.1021/acs.jproteome.9b00245 | SDG/關鍵字: | acadm protein; aurora A kinase; aurora B kinase; aurora kinase; aurora kinase inhibitor; flavoprotein; mitochondrial enzyme; oncoprotein; tozasertib; unclassified drug; acyl coenzyme A dehydrogenase; aurora kinase; N Myc proto oncogene protein; piperazine derivative; protein kinase inhibitor; tozasertib; animal experiment; animal model; animal tissue; Article; cancer inhibition; cancer survival; carbohydrate metabolism; cell cycle arrest; cell migration; cell proliferation; controlled study; event free survival; fatty acid metabolism; fatty acid oxidation; gene amplification; gene expression level; human; human cell; metabolism; mouse; neuroblastoma; neuroblastoma cell line; nonhuman; oncogene c myb; overall survival; priority journal; proteomics; quantitative analysis; transcriptomics; transgenic mouse; tumor invasion; 129 mouse; animal; disease exacerbation; drug effect; gene expression profiling; gene expression regulation; genetics; metabolism; neuroblastoma; procedures; proteomics; survival analysis; tumor cell line; Acyl-CoA Dehydrogenase; Animals; Aurora Kinases; Cell Line, Tumor; Cell Proliferation; Disease Progression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Metabolic Networks and Pathways; Mice, 129 Strain; Mice, Transgenic; N-Myc Proto-Oncogene Protein; Neuroblastoma; Piperazines; Protein Kinase Inhibitors; Proteomics; Survival Analysis |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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