A Combined Proteomics and Metabolomics Profiling of Gastric Cardia Cancer Reveals Characteristic Dysregulations in Glucose Metabolism
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 appr...
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| Published in: | Molecular & cellular proteomics Vol. 9; no. 12; pp. 2617 - 2628 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01-12-2010
The American Society for Biochemistry and Molecular Biology |
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| 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. |
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| AbstractList | 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. 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. |
| Author | Li, Wen-Jie Jia, Wei Xie, Dong Qiu, Yun-Ping Li, En-Ming Xu, Li-Yan Tam, Jason P.M. Li, Jing-Jing Chen, Ping-Ping Qi, Robert Z. Zhao, Jiang-Sha Wang, Xiao-Yan Cai, Zhen Peng, Dan-Ni Chen, Tian-Lu |
| Author_xml | – sequence: 1 givenname: Zhen surname: Cai fullname: Cai, Zhen organization: ‡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 – sequence: 2 givenname: Jiang-Sha surname: Zhao fullname: Zhao, Jiang-Sha organization: ‡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 – sequence: 3 givenname: Jing-Jing surname: Li fullname: Li, Jing-Jing organization: ‡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 – sequence: 4 givenname: Dan-Ni surname: Peng fullname: Peng, Dan-Ni organization: ‡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 – sequence: 5 givenname: Xiao-Yan surname: Wang fullname: Wang, Xiao-Yan organization: ¶Shanghai Center for Systems Biomedicine and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China – sequence: 6 givenname: Tian-Lu surname: Chen fullname: Chen, Tian-Lu organization: ¶Shanghai Center for Systems Biomedicine and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China – sequence: 7 givenname: Yun-Ping surname: Qiu fullname: Qiu, Yun-Ping organization: ¶Shanghai Center for Systems Biomedicine and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China – sequence: 8 givenname: Ping-Ping surname: Chen fullname: Chen, Ping-Ping organization: ‖College of Public Health, Zhengzhou University, Zhengzhou 450001, China – sequence: 9 givenname: Wen-Jie surname: Li fullname: Li, Wen-Jie organization: ‖College of Public Health, Zhengzhou University, Zhengzhou 450001, China – sequence: 10 givenname: Li-Yan surname: Xu fullname: Xu, Li-Yan organization: Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China – sequence: 11 givenname: En-Ming surname: Li fullname: Li, En-Ming organization: Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, China – sequence: 12 givenname: Jason P.M. surname: Tam fullname: Tam, Jason P.M. organization: ‡‡Department of Biochemistry, Hong Kong University of Sciences and Technology, HongKong, China – sequence: 13 givenname: Robert Z. surname: Qi fullname: Qi, Robert Z. organization: ‡‡Department of Biochemistry, Hong Kong University of Sciences and Technology, HongKong, China – sequence: 14 givenname: Wei surname: Jia fullname: Jia, Wei email: w_jia@uncg.edu organization: ¶Shanghai Center for Systems Biomedicine and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China – sequence: 15 givenname: Dong surname: Xie fullname: Xie, Dong email: dxie@sibs.ac.cn organization: ‡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 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20699381$$D View this record in MEDLINE/PubMed |
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| Copyright | 2010 © 2010 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. 2010 by The American Society for Biochemistry and Molecular Biology, Inc. 2010 |
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| Snippet | Gastric cardia cancer (GCC), which occurs at the gastric-esophageal boundary, is one of the most malignant tumors. Despite its high mortality and morbidity,... |
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| SubjectTerms | Base Sequence Cell Line, Tumor Chromatography, High Pressure Liquid Citric Acid Cycle DNA Primers Electrophoresis, Gel, Two-Dimensional Female Glucose - metabolism Glycolysis Humans L-Lactate Dehydrogenase - genetics Male Metabolomics Middle Aged Polymerase Chain Reaction Proteomics Pyruvate Dehydrogenase Complex - genetics RNA Interference Stomach Neoplasms - enzymology Stomach Neoplasms - metabolism Stomach Neoplasms - pathology |
| Title | A Combined Proteomics and Metabolomics Profiling of Gastric Cardia Cancer Reveals Characteristic Dysregulations in Glucose Metabolism |
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