The Reverse Warburg Effect is Associated with Fbp2-Dependent Hif1α Regulation in Cancer Cells Stimulated by Fibroblasts.
fructose 1,6-bisphosphatase 2
glycolysis
hypoxia-inducible factor-1α
lung cancer
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
14 01 2020
14 01 2020
Historique:
received:
20
11
2019
revised:
02
01
2020
accepted:
09
01
2020
entrez:
18
1
2020
pubmed:
18
1
2020
medline:
9
2
2021
Statut:
epublish
Résumé
Fibroblasts are important contributors to cancer development. They create a tumor microenvironment and modulate our metabolism and treatment resistance. In the present paper, we demonstrate that healthy fibroblasts induce metabolic coupling with non-small cell lung cancer cells by down-regulating the expression of glycolytic enzymes in cancer cells and increasing the fibroblasts' ability to release lactate and thus support cancer cells with energy-rich glucose-derived metabolites, such as lactate and pyruvate-a process known as the reverse Warburg effect. We demonstrate that these changes result from a fibroblasts-stimulated increase in the expression of fructose bisphosphatase (Fbp) in cancer cells and the consequent modulation of Hif1α function. We show that, in contrast to current beliefs, in lung cancer cells, the predominant and strong interaction with the Hif1α form of Fbp is not the liver (Fbp1) but in the muscle (Fbp2) isoform. Since Fbp2 oligomerization state and thus, its role is regulated by AMP and NAD
Identifiants
pubmed: 31947613
pii: cells9010205
doi: 10.3390/cells9010205
pmc: PMC7016812
pii:
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
FBP2 protein, human
EC 3.1.3.11
Fructose-Bisphosphatase
EC 3.1.3.11
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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