A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism

Zhen Cai, Jiang Sha Zhao, Jing Jing Li, Dan Ni Peng, Xiao Yan Wang, Tian Lu Chen, Yunping Qiu, Ping Ping Chen, Wen Jie Li, Li Yan Xu, En Ming Li, Jason P M Tam, Robert Z. Qi, Wei Jia, Dong Xie

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Gastric cardia cancer (GCC), which occurs at the gastricesophageal 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.

Original languageEnglish (US)
Pages (from-to)2617-2628
Number of pages12
JournalMolecular and Cellular Proteomics
Volume9
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Cardia
Metabolomics
Pyruvic Acid
Metabolism
Proteomics
Stomach Neoplasms
Glucose
Citric Acid Cycle
Glycolysis
Oxidoreductases
Cell growth
Enzymes
Cell Movement
Disease Progression
Tumors
Down-Regulation
Cells
Morbidity
Mortality
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. / Cai, Zhen; Zhao, Jiang Sha; Li, Jing Jing; Peng, Dan Ni; Wang, Xiao Yan; Chen, Tian Lu; Qiu, Yunping; Chen, Ping Ping; Li, Wen Jie; Xu, Li Yan; Li, En Ming; Tam, Jason P M; Qi, Robert Z.; Jia, Wei; Xie, Dong.

In: Molecular and Cellular Proteomics, Vol. 9, No. 12, 12.2010, p. 2617-2628.

Research output: Contribution to journalArticle

Cai, Z, Zhao, JS, Li, JJ, Peng, DN, Wang, XY, Chen, TL, Qiu, Y, Chen, PP, Li, WJ, Xu, LY, Li, EM, Tam, JPM, Qi, RZ, Jia, W & Xie, D 2010, 'A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism', Molecular and Cellular Proteomics, vol. 9, no. 12, pp. 2617-2628. https://doi.org/10.1074/mcp.M110.000661
Cai, Zhen ; Zhao, Jiang Sha ; Li, Jing Jing ; Peng, Dan Ni ; Wang, Xiao Yan ; Chen, Tian Lu ; Qiu, Yunping ; Chen, Ping Ping ; Li, Wen Jie ; Xu, Li Yan ; Li, En Ming ; Tam, Jason P M ; Qi, Robert Z. ; Jia, Wei ; Xie, Dong. / A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. In: Molecular and Cellular Proteomics. 2010 ; Vol. 9, No. 12. pp. 2617-2628.
@article{d5b9cf6792944769a85f40cbaabdfe3b,
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 gastricesophageal 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.",
author = "Zhen Cai and Zhao, {Jiang Sha} and Li, {Jing Jing} and Peng, {Dan Ni} and Wang, {Xiao Yan} and Chen, {Tian Lu} and Yunping Qiu and Chen, {Ping Ping} and Li, {Wen Jie} and Xu, {Li Yan} and Li, {En Ming} and Tam, {Jason P M} and Qi, {Robert Z.} and Wei Jia and Dong Xie",
year = "2010",
month = "12",
doi = "10.1074/mcp.M110.000661",
language = "English (US)",
volume = "9",
pages = "2617--2628",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism

AU - Cai, Zhen

AU - Zhao, Jiang Sha

AU - Li, Jing Jing

AU - Peng, Dan Ni

AU - Wang, Xiao Yan

AU - Chen, Tian Lu

AU - Qiu, Yunping

AU - Chen, Ping Ping

AU - Li, Wen Jie

AU - Xu, Li Yan

AU - Li, En Ming

AU - Tam, Jason P M

AU - Qi, Robert Z.

AU - Jia, Wei

AU - Xie, Dong

PY - 2010/12

Y1 - 2010/12

N2 - Gastric cardia cancer (GCC), which occurs at the gastricesophageal 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.

AB - Gastric cardia cancer (GCC), which occurs at the gastricesophageal 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.

UR - http://www.scopus.com/inward/record.url?scp=78650138387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650138387&partnerID=8YFLogxK

U2 - 10.1074/mcp.M110.000661

DO - 10.1074/mcp.M110.000661

M3 - Article

C2 - 20699381

AN - SCOPUS:78650138387

VL - 9

SP - 2617

EP - 2628

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 12

ER -