FBP1 enhances the radiosensitivity by suppressing glycolysis via the FBXW7/mTOR axis in nasopharyngeal carcinoma cells.
Life Sci
; 283: 119840, 2021 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-34298040
ABSTRACT
AIMS:
The high glycolysis state of tumor cells is closely related to radioresistance. Fructose-1,6-bisphosphatase (FBP1) can regulate aerobic glycolysis and exerts tumor suppressor effects in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains to be investigated. MATERIALS ANDMETHODS:
RT-qPCR was used to measure FBP1 mRNA level. Glucose consumption, lactic acid production and ATP level was determined to evaluate glycolysis. The sensitivity of NPC cells to radiation was analyzed by MTT assay. Apoptosis was performed using flow cytometry. Gain- and loss-of function assays were carried out to explore the specific role of FBP1 and FBXW7 (F-box and WD repeat domain-containing 7) in NPC cell functions. The interactions between FBXW7 and FBP1 or mTOR were validated with co-immunoprecipitation assay. The in vivo experiments with xenografts were used to evaluate the role of FBP1 in tumor growth. KEYFINDINGS:
FBP1 expression was lower in NPC tissues and cells than in normal controls and nasopharyngeal epithelial cells. Human recombinant FBP1 (rh-FBP1) treatment suppressed glycolysis in NPC cells. Besides, silencing FBP1 weakened the radiosensitivity and alleviated radiation-induced apoptosis and DNA damage by promoting glycolysis. Mechanism exploration found that FBP1 promoted FBXW7 protein level through suppressing the autoubiquitination of FBXW7. Then, FBXW7 restrained mTOR level by facilitating mTOR ubiquitination, thereby suppressing glycolysis and promoting radiation-induced apoptosis and DNA damage. Furthermore, overexpressing FBP1 in vivo hindered tumor growth and enhanced the antitumor activity of radiation.SIGNIFICANCE:
FBP1 promoted the radiosensitivity in NPC cells by inhibiting glycolysis through the FBXW7/mTOR axis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tolerancia a Radiación
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Transducción de Señal
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Neoplasias Nasofaríngeas
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Serina-Treonina Quinasas TOR
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Proteína 7 que Contiene Repeticiones F-Box-WD
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Carcinoma Nasofaríngeo
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Glucólisis
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Proteínas de Neoplasias
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Life Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
China