Proteomics

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Quantitative proteomics and bioinformatics analyses reveal the mechanism of pan-aurora kinase inhibitor tozasertib in neuroblastoma


ABSTRACT: Neuroblastoma is the third most common pediatric cancer and is responsible for approximately 15% of all childhood cancer deaths (Maris & Matthay, 1999). In our analysis, we found that poor patient survival with increasing mRNA expression level of AURKA and AURKB in Mycn-amplified neuroblastoma. In the light of this evidence, we were able to find possibilities of existing inhibitors for therapy. According to the following experiments, we found that tozasertib, a pan-Aurora kinase inhibitor, has high therapeutic potential in neuroblastoma treatment. First, we performed in vitro experiments to reveal that tozasertib suppressed cell proliferation in multiple Mycn-amplified neuroblastoma cell lines. Next, we evaluated ex vivo not only in Mycn-amplified neuroblastoma xenograft mouse model but also TH-Mycn transgenic mouse model. The results showed that tozasertib significantly inhibited the tumor growth and prolonged the survival probability in both animal models. Finally, we explored the mechanism of tozasertib-treated tissues in two animal models by iTRAQ proteomic.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Neuroblastoma Cell Line, Neuroblastoma Cell

DISEASE(S): Neuroblastoma

SUBMITTER: Chiao-Hui Hsieh  

LAB HEAD: Hsueh-Fen Juan

PROVIDER: PXD007640 | Pride | 2019-09-30

REPOSITORIES: pride

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10_151201.msf Msf
10_151201.raw Raw
12_151201.msf Msf
12_151201.raw Raw
13_151201.msf Msf
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Publications

Quantitative Proteomics of Th-MYCN Transgenic Mice Reveals Aurora Kinase Inhibitor Altered Metabolic Pathways and Enhanced ACADM To Suppress Neuroblastoma Progression.

Hsieh Chiao-Hui CH   Cheung Chantal Hoi Yin CHY   Liu Yen-Lin YL   Hou Chun-Li CL   Hsu Chia-Lang CL   Huang Chen-Tsung CT   Yang Tsai-Shan TS   Chen Sung-Fang SF   Chen Chiung-Nien CN   Hsu Wen-Ming WM   Huang Hsuan-Cheng HC   Juan Hsueh-Fen HF  

Journal of proteome research 20191011 11


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-r  ...[more]

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