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. Molecular & Cellular Proteomics 9: 2617-2628, 2010.

Effects of growth hormone on the salmon pituitary proteome

“…In comparison with proliferating cells, quiescent cells exhibit a decrease in expression of glycolytic enzymes and an increase in expression of OXPHOS related enzymes [36][37][38]. In this study, we observed down-regulation of ALDOC, TPI1, and GAPDH, and upregulation of ATP5B in the excess GH1-treated pituitary ( Table 2).…”

Cell Metabolomics

“…The focus on the metabolic profile of the whole organism provides relevant information about specific cell types under different conditions, which is crucial for a more holistic understanding of cell properties and functions (Cai et al, 2010;Mintz-Oron et al, 2012). By using a combination of feature selection, pattern recognition, and multivariate data analysis approaches, metabolomic profiling aims to provide a comprehensive assessment of the alterations in the metabolite levels in cells (Lange et al, 2011;Stringari et al, 2011;Turnbaugh et al, 2011).…”

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

“…Combining proteomics analysis with metabolic profiling is especially attractive, since metabolomics provides information in forming a functional interpretation of proteomics data, while proteomics analysis contributes to a better understanding of metabolomics data by highlighting participating enzymes and/or enzymatic pathways. The combination of proteomics and metabolomics has aided in elucidating the molecular mechanisms of various disorders, including cancer (Cai et al, 2010;Ma et al, 2012), psychiatric disorders Wesseling et al, 2013;Zhang et al, 2011), and cardiovascular disease (Mayr et al, 2008). Among these studies combining proteomics and metabolomics approaches, one research group has identified biomarker candidates and hippocampal metabolic changes with paroxetine treatment (Webhofer et al, 2012).…”