Ketohexokinase-A deficiency attenuates the proliferation via reducing ß-catenin in gastric cancer cells.
Exp Cell Res
; 438(1): 114038, 2024 May 01.
Article
en En
| MEDLINE
| ID: mdl-38614422
ABSTRACT
Overconsumption of fructose is closely related to cancer. Ketohexokinase (KHK) catalyzes the conversion from fructose to fructose-1-phosphate (F1P), which is the first and committed step of fructose metabolism. Recently, aberrant KHK activation has been identified in multiple malignancies. However, the roles of KHK in gastric cancer (GC) cells are largely unclear. Herein, we reveal that the expression of ketohexokinase-A (KHK-A), one alternatively spliced KHK isoform that possesses low affinity for fructose, was markedly increased in GC cells. Depletion of endogenous KHK-A expression using lentiviruses encoding short hairpin RNAs (shRNAs) or pharmaceutical disruption of KHK-A activity using KHK-IN-1 hydrochloride in GC NCI-N87 and HGC-27 cells inhibited the proliferation in vitro and in vivo. Additionally, the mitochondrial respiration in the GC cells with KHK-A deficiency compared with the control cells was significantly impaired. One commercially-available antibody array was used to explore the effects of KHK-A knockdown on signaling pathways, showing that ß-catenin was remarkably reduced in the KHK-A deficient GC cells compared with the control ones. Pharmaceutical reduction in ß-catenin levels slowed down the proliferation of GC cells. These data uncover that KHK-A promotes the proliferation in GC cells, indicating that this enzyme might be a promising therapeutical target for GC treatment.
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Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Proliferación Celular
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Beta Catenina
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Fructoquinasas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
China