title: Crosstalk among proteome, acetylome and succinylome in colon cancer HCT116 cell treated with sodium dichloroacetate.
abstract: Protein lysine acetylation and succinylation play important regulatory roles in cells, both of which or each other has a close relationship. Dichloroacetate (DCA), a well-known pyruvate dehydrogenase kinase (PDK) inhibitor, has the potential to be used as anti-cancer drugs for several tumors including colorectal cancer. However, little is known about the potential mechanism of DCA-based cancer therapy by protein posttranslational modifications (PTM) including global proteome, acetylome and succinylome. Here the combinations with stable isotope labeling (SILAC), antibody affinity enrichment and high resolution LC-MS/MS analysis were performed in human colon cancer HCT116 cells. The quantifiable proteome was annotated using bioinformatics. In total, 4,518 proteins, 1,436 acetylation sites, and 671 succinylation sites were quantified, respectively to DCA treatment. Among the quantified acetylated sites, 158 were with increased level (quantification ratio >1.5) and 145 with decreased level (quantification ratio <0.67). Meanwhile, 179 up-regulated and 114 down-regulated succinylated sites were identified. The bioinformatics analyses initially showed acetylation and succinylation were involved in a wide range of cellular functions upon DCA-based anti-cancer effects. Notably, protein-protein interaction network analyses demonstrated widespread interactions modulated by protein acetylation and succinylation. Taken together, this study may shed a light on understanding the mechanism of DCA-based cancer treatment.
authors.affiliation: Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Danxi
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, Shanghai, 200060, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Suzhou Science &Technology Town Hospital, Suzhou, 215000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Fudan University Shanghai Cancer Center, Cancer institute, Shanghai, 200230, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000595:Amino Acid Sequence; D002952:Citric Acid Cycle / Q000187:drug effects; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000378:metabolism*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D013386:Succinates; D003999:Dichloroacetic Acid; D008239:Lysine