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NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
Szymura, Szymon J; Zaemes, Jacob P; Allison, David F; Clift, Sheena H; D'Innocenzi, Jaclyn M; Gray, Lisa G; McKenna, Brian D; Morris, Benjamin B; Bekiranov, Stefan; LeGallo, Robin D; Jones, David R; Mayo, Marty W.
Afiliação
  • Szymura SJ; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Zaemes JP; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Allison DF; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Clift SH; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • D'Innocenzi JM; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Gray LG; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • McKenna BD; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Morris BB; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Bekiranov S; Department of Pathology, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • LeGallo RD; Department of Biochemistry & Molecular Genetics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Jones DR; Department of Pathology, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908, USA.
  • Mayo MW; Professor & Chief, Thoracic Surgery Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 7, New York, NY, 10065, USA.
Cell Commun Signal ; 17(1): 24, 2019 03 18.
Article em En | MEDLINE | ID: mdl-30885209
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC). While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed. Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2). GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT). METHODS: Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC. Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion. RESULTS: Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6. Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT. CONCLUSIONS: Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC. Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: NF-kappa B / Carcinoma Pulmonar de Células não Pequenas / Sirtuínas / Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante) / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: NF-kappa B / Carcinoma Pulmonar de Células não Pequenas / Sirtuínas / Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante) / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article