NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer Journal Article

Authors: Szymura, S. J.; Zaemes, J. P.; Allison, D. F.; Clift, S. H.; D'Innocenzi, J. M.; Gray, L. G.; McKenna, B. D.; Morris, B. B.; Bekiranov, S.; Legallo, R. D.; Jones, D. R.; Mayo, M. W.
Article Title: NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer
Abstract: 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. [Figure not available: see fulltext.]. © 2019 The Author(s).
Keywords: cell migration; epithelial-mesenchymal transition; non-small cell lung cancer (nsclc); glutamine-fructose-6-phosphate transaminase 2 (gfpt2); nuclear factor kappa b (nf-κb); sirtuin-6 (sirt6)
Journal Title: Cell Communication and Signaling
Volume: 17
ISSN: 1478-811X
Publisher: BioMed Central Ltd.  
Date Published: 2019-03-18
Start Page: 24
Language: English
DOI: 10.1186/s12964-019-0335-5
PUBMED: 30885209
PROVIDER: scopus
PMCID: PMC6421657
Notes: Source: Scopus
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MSK Authors
  1. David Randolph Jones
    204 Jones