Fructose-1,6-bisphosphatase 1 suppresses PPARα-mediated gene transcription and non-small-cell lung cancer progression.
FBP1
O-GlcNAcylation
glutamine deprivation
non-small cell lung cancer (NSCLC)
phosphorylation
prognostic biomarker
Journal
American journal of cancer research
ISSN: 2156-6976
Titre abrégé: Am J Cancer Res
Pays: United States
ID NLM: 101549944
Informations de publication
Date de publication:
2023
2023
Historique:
received:
01
07
2023
accepted:
18
09
2023
medline:
16
11
2023
pubmed:
16
11
2023
entrez:
16
11
2023
Statut:
epublish
Résumé
Rapidly growing tumors often encounter energy stress, such as glutamine deficiency. However, how normal and tumor cells differentially respond to glutamine deficiency remains largely unclear. Here, we demonstrate that glutamine deprivation activates PERK, which phosphorylates FBP1 at S170 and induces nuclear accumulation of FBP1. Nuclear FBP1 inhibits PPARα-mediated β-oxidation gene transcription in normal lung epithelial cells. In contrast, highly expressed OGT in non-small cell lung cancer (NSCLC) cells promotes FBP1 O-GlcNAcylation, which abrogates FBP1 phosphorylation and enhances β-oxidation gene transcription to support cell proliferation under glutamine deficiency. In addition, FBP1 pS170 is negatively correlated with OGT expression in human NSCLC specimens, and low expression of FBP1 pS170 is associated with poor prognosis in NSCLC patients. These findings highlight the differential regulation of FBP1 in normal and NSCLC cells under glutamine deprivation and underscore the potential to target nuclear FBP1 for NSCLC treatment.
Types de publication
Journal Article
Langues
eng
Pagination
4742-4754Informations de copyright
AJCR Copyright © 2023.
Déclaration de conflit d'intérêts
Z.L. owns shares in Signalway Biotechnology (Pearland, TX), which supplied rabbit antibodies that recognize FBP1 pS170.
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