Oncotarget

Research Papers:

YBX1 promotes tumor growth by elevating glycolysis in human bladder cancer

Liuyu Xu, Hongyun Li, Longchao Wu and Shiming Huang _

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Oncotarget. 2017; 8:65946-65956. https://doi.org/10.18632/oncotarget.19583

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Abstract

Liuyu Xu1, Hongyun Li1, Longchao Wu2 and Shiming Huang1

1Department of Urology, QianFoShan Hospital Affiliated to Shandong University, Jinan 250014, P. R. China

2Department of Urology, Penglai People’s Hospital of Shandong, Penglai 265600, P. R. China

Correspondence to:

Shiming Huang, email: Doctorhsm@163.com

Keywords: YB-1, Warburg effect, The Cancer Genome Atlas, bladder cancer

Received: April 27, 2017    Accepted: June 28, 2017    Published: July 26, 2017

ABSTRACT

Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR). Inhibition of glycolysis completely compromises the tumor-promoting effect of YBX1 on tumor growth. Mechanistically, YBX1 regulates the expression of c-Myc and HIF1α, which further upregulate glycolytic enzymes to facilitate glycolysis. Moreover, in vivo study further confirms that genetic silencing of YBX1 markedly attenuates tumor growth and this tumor-suppressive effect is largely dependent on reduced glycolysis. Taken together, these results, as a proof of principle, provide a novel insight into the oncogenic role of YBX1 in glycolysis and suggest the potential therapeutic strategy by targeting YBX1 in bladder cancer.


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