Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma.
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.
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Xiao
X
Gu
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Zhongyan
Z
Hua
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Yudi
Y
Dong
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Yue
Y
Zhan
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Xiaowen
X
Zhang
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Wei
W
Tian
Cellular &Molecular Biology Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Zhihui
Z
Liu
Cellular &Molecular Biology Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Carol J
CJ
Thiele
Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Zhijie
Z
Li
D000107:Acetylation; D000596:Amino Acids; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D008239:Lysine / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020543:Proteome / Q000032:analysis*; D053719:Tandem Mass Spectrometry
D000596:Amino Acids; D000970:Antineoplastic Agents; D020543:Proteome; D010767:Phosphorylcholine; C105905:perifosine; D008239:Lysine