Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma.

Abstract

Perifosine, an Akt inhibitor, has been shown to be effective in controlling neuroblastoma tumor growth. However, studies indicate that in addition to the ability to inhibit Akt, other mechanisms contribute to perifosine's anti-tumor activity. To gain insight into perifosine anti-tumor activity in neuroblastoma we have studied changes in the proteome and acetylome after perifosine treatment in SK-N-AS neuroblastoma cells using SILAC labeling, affinity enrichment, high-resolution and LC-MS/MS analysis. Bioinformatic analysis indicates that, a total of 5,880 proteins and 3,415 lysine acetylation sites were quantified in SK-N-AS cells and 216 differentially expressed proteins and 115 differentially expressed lysine acetylation sites were obtained. These differentially expressed proteins and lysine acetylated proteins were involved in a number of different biological functions, metabolic pathways and pathophysiological processes. This study details the impact of perifosine on proteome and lysine acetylome in SK-N-AS cells and expands our understanding of the mechanisms of perifosine action in neuroblastoma.

• Authors: Xiao Gu, Zhongyan Hua, Yudi Dong, Yue Zhan, Xiaowen Zhang, Wei Tian, Zhihui Liu, Carol J Thiele, Zhijie Li
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 42062 (02 06 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28165023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Antineoplastic Agents
• Proteome
• Phosphorylcholine
• perifosine
• Lysine

Topics

• Acetylation
• Amino Acids
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Chromatography, Liquid
• Humans
• Lysine (metabolism)
• Metabolic Networks and Pathways
• Neuroblastoma (drug therapy, genetics)
• Phosphorylcholine (analogs & derivatives, pharmacology)
• Proteome (analysis)
• Tandem Mass Spectrometry