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Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade
Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 37, Iss 1, Pp 1-11 (2018), Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Background Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. Methods Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression. Loss- and gain-of function assays were performed to investigate the role of Chibby in NPC cells. Western blot, cell proliferation, Glucose uptake, Lactate release, ATP level, and O2 consumption assays were used to determine the mechanism of Chibby regulation of underlying targets. Finally, immunohistochemistry assay of fresh NPC and nasopharyngeal normal tissue sample were used to detect the expression of Chibby, β-Catenin, and PDK1 by immunostaining. Results We observed that Chibby, a β-catenin-associated antagonist, is down-regulated in nasopharyngeal carcinoma cell lines and inhibits Wnt/β-Catenin signaling induced Warburg effect. Mechanism study revealed that Chibby regulates aerobic glycolysis in NPC cells through pyruvate dehydrogenase kinase 1(PDK1), an important enzyme involved in glucose metabolism. Moreover, Chibby suppresses aerobic glycolysis of NPC via Wnt/β-Catenin-Lin28/let7-PDK1 cascade. Chibby and PDK1 are critical for Wnt/β-Catenin signaling induced NPC cell proliferation both in vitro and in vivo. Finally, immunostaining assay of tissue samples provides an important clinical relevance among Chibby, Wnt/β-Catenin signaling and PDK1. Conclusions Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/β-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-018-0769-4) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Cancer Research
Pyruvate dehydrogenase kinase
Protein Serine-Threonine Kinases
LIN28
lcsh:RC254-282
03 medical and health sciences
Mice
0302 clinical medicine
Wnt/β-Catenin signaling
Cell Line, Tumor
otorhinolaryngologic diseases
medicine
Nasopharyngeal carcinoma
Animals
Humans
beta Catenin
Cell Proliferation
Chemistry
Cell growth
Research
Wnt signaling pathway
Nuclear Proteins
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
RNA-Binding Proteins
Chibby
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Warburg effect
Immunohistochemistry
Aerobiosis
Wnt Proteins
Disease Models, Animal
MicroRNAs
030104 developmental biology
Oncology
Anaerobic glycolysis
030220 oncology & carcinogenesis
Catenin
Cancer research
Heterografts
Female
Carrier Proteins
Glycolysis
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 37
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....d9baad0cb0e0038ae1196b1f2aa40112
- Full Text :
- https://doi.org/10.1186/s13046-018-0769-4