title: Global-scale profiling of differential expressed lysine acetylated proteins in colorectal cancer tumors and paired liver metastases.
abstract: 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.
  
  
  
  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.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China.
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Peking University Health Science Center, Beijing 100191, PR China.
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki 00290, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.affiliation: Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki 00290, Finland.
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
authors.affiliation: Jingjie PTM Biolab (Hangzhou) Co. Ltd, Hangzhou 310018, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China. Electronic address: yeyingjiang@pkuph.edu.cn.
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China. Electronic address: shanwang60@sina.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008239:Lysine / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D008239:Lysine
keywords: Colorectal cancer; Liver metastasis; Lysine acetylation; PTMs