Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation
| Autor: | Catherine E. Costello, Katia C. Gondim, Stephen A. Whelan, Miguel C. Lucena, Monica M. Marinho-Carvalho, Isadora A. Oliveira, Wagner B. Dias, Adriane R. Todeschini, Iron F. De Paula, Patricia Carvalho-cruz, Mauro Sola-Penna, Mark E. McComb, Rafaela Muniz de Queiroz, Joana L. Donadio |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Glycosylation Glucose uptake Glycobiology and Extracellular Matrices Biology Pentose phosphate pathway N-Acetylglucosaminyltransferases Biochemistry 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate Transforming Growth Factor beta Cell Line Tumor Pyruvic Acid Humans Glycolysis Lactic Acid Epithelial–mesenchymal transition Molecular Biology Fucosylation Hexosamines Cell Biology Biosynthetic Pathways Cell biology carbohydrates (lipids) Metabolic pathway Glucose 030104 developmental biology chemistry Enzyme Induction Protein Processing Post-Translational Flux (metabolism) Glycogen |
| Zdroj: | Journal of Biological Chemistry. 291:12917-12929 |
| ISSN: | 0021-9258 |
| Popis: | Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2–5% of the total glucose, generating UDP-GlcNAc as the end product. UDP-GlcNAc is the donor substrate used in multiple glycosylation reactions. Thus, HBP links the altered metabolism with aberrant glycosylation providing a mechanism for cancer cells to sense and respond to microenvironment changes. Here, we investigate the changes of glucose metabolism during epithelial mesenchymal transition (EMT) and the role of O-GlcNAcylation in this process. We show that A549 cells increase glucose uptake during EMT, but instead of increasing the glycolysis and pentose phosphate pathway, the glucose is shunted through the HBP. The activation of HBP induces an aberrant cell surface glycosylation and O-GlcNAcylation. The cell surface glycans display an increase of sialylation α2–6, poly-LacNAc, and fucosylation, all known epitopes found in different tumor models. In addition, modulation of O-GlcNAc levels was demonstrated to be important during the EMT process. Taken together, our results indicate that EMT is an applicable model to study metabolic and glycophenotype changes during carcinogenesis, suggesting that cell glycosylation senses metabolic changes and modulates cell plasticity. |
| Databáze: | OpenAIRE |
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