Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases
Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases
复制标题
结直肠癌肿瘤和配对肝转移中差异表达的赖氨酸乙酰化蛋白的全球范围分析
DOI：
10.1016/j.jprot.2016.05.002
复制
发表时间：
2016-06-16
影响因子：
3.3
通讯作者：
Wang, Shan
中科院分区：
文献类型：
--
作者：
Shen, Zhanlong;Wang, Bo;Wang, Shan
赖氨酸乙酰化修饰对结直肠癌的远处转移有影响。然而，结直肠癌中乙酰化蛋白的总体分布以及结直肠癌原发灶和远处转移灶之间乙酰化蛋白和乙酰化位点的差异表达尚不清楚。我们的目的是建立一个完整的乙酰组图谱在结直肠癌和配对肝转移。结合高亲和力乙酰化肽富集和高灵敏度质谱分析，从316个蛋白质中鉴定出603个乙酰化位点，其中462个乙酰化位点对应于243个蛋白质。根据细胞组成、分子功能和生物学过程对它们进行了分类，并分析了它们的代谢途径、结构域结构和蛋白质相互作用网络。最后，我们评估了差异表达的赖氨酸乙酰化位点，发现与原发性CRC相比，22种蛋白质的31个乙酰化位点在CRC肝转移中下调，而32种蛋白质的40个乙酰化位点上调，其中HIST 2H3 AK 19 Ac和H2 BLK 121 Ac是变化最大的乙酰化组蛋白，而TPM2 K152Ac和ADH 1B K331Ac是改变最多的乙酰化非组蛋白。这些结果提供了一个扩展的理解乙酰组在CRC及其远处转移，并可能证明适用于转移性CRC.Biological意义的分子靶向治疗：本研究描述的第一次，即全规模的赖氨酸乙酰化蛋白质的分析，确定和量化的结直肠癌（CRC）和配对的肝转移。这项研究的新奇在于我们构建了一个完整的乙酰组图谱在CRC和配对肝转移。并从细胞组成、分子功能和生物学过程等方面对这些差异表达的乙酰化蛋白进行了分析。此外，还对乙酰化蛋白的代谢途径、结构域结构和蛋白质相互作用网络进行了研究。我们的方法表明，差异表达的蛋白质，HIST 2H3 AK19 Ac和H2 BLK121 Ac是乙酰化组蛋白的变化最大，而TPM2 K152 Ac和ADH 1B K331 Ac是乙酰化非组蛋白的变化最大。我们的研究结果提供了一个扩展的理解乙酰组在结直肠癌及其远处转移，并可能证明适用于转移性结直肠癌的分子靶向治疗。(C)2016爱思唯尔B.V.保留所有权利。
Lysine acetylated modification was indicated to impact colorectal cancer (CRC)'s distant metastasis. However, the global acetylated proteins in CRC and the differential expressed acetylated proteins and acetylated sites between CRC primary and distant metastatic tumor remains unclear. Our aim was to construct a complete atlas of acetylome in CRC and paired liver metastases. Combining high affinity enrichment of acetylated peptides with high sensitive mass spectrometry, we identified 603 acetylation sites from 316 proteins, among which 462 acetylation sites corresponding to 243 proteins were quantified. We further classified them into groups according to cell component, molecular function and biological process and analyzed the metabolic pathways, domain structures and protein interaction networks. Finally, we evaluated the differentially expressed lysine acetylation sites and revealed that 31 acetylated sites of 22 proteins were downregulated in CRC liver metastases compared to that in primary CRC while 40 acetylated sites of 32 proteins were upregulated, of which HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. These results provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC.Biological significance: This study described provides, for the first time, that full-scale profiling of lysine acetylated proteins were identified and quantified in colorectal cancer (CRC) and paired liver metastases. The novelty of the study is that we constructed a complete atlas of acetylome in CRC and paired liver metastases. Moreover, we analyzed these differentially expressed acetylated proteins in cell component, molecular function and biological process. In addition, metabolic pathways, domain structures and protein interaction networks of acetylated proteins were also investigated. Our approaches shows that of the differentially expressed proteins, HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. Our findings provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. (C) 2016 Elsevier B.V. All rights reserved.