Back to Search Start Over

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

Authors :
Qi-Cong Luo
Chengfu Cai
Mao-Li Chen
Wang-Yu Cai
Yanjun Mi
Guo-Dong Ye
Dong-Yan Shen
Chen Xinxin
Han Daxiong
Wei Zhang
Shu-Yu Yang
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.

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