title: A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism.
abstract: Gastric cardia cancer (GCC), which occurs at the gastric-esophageal boundary, is one of the most malignant tumors. Despite its high mortality and morbidity, the molecular mechanism of initiation and progression of this disease is largely unknown. In this study, using proteomics and metabolomics approaches, we found that the level of several enzymes and their related metabolic intermediates involved in glucose metabolism were deregulated in GCC. Among these enzymes, two subunits controlling pyruvic acid efflux, lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase B (PDHB), were further analyzed in vitro. Either down-regulation of LDH subunit LDHA or overexpression of PDH subunit PDHB could force pyruvic acid into the Krebs cycle rather than the glycolysis process in AGS gastric cancer cells, which inhibited cell growth and cell migration. Our results reflect an important glucose metabolic signature, especially the dysregulation of pyruvic acid efflux in the development of GCC. Forced transition from glycolysis to the Krebs cycle had an inhibitory effect on GCC progression, providing potential therapeutic targets for this disease.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.forename: Jiang-Sha
authors.initials: JS
authors.lastname: Zhao
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Dan-Ni
authors.initials: DN
authors.lastname: Peng
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Chen
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Qiu
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Chen
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Li
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
authors.forename: En-Ming
authors.initials: EM
authors.lastname: Li
authors.forename: Jason P M
authors.initials: JP
authors.lastname: Tam
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D002952:Citric Acid Cycle; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D040901:Proteomics; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D017931:DNA Primers; D011768:Pyruvate Dehydrogenase Complex; D007770:L-Lactate Dehydrogenase; D005947:Glucose