RT Journal Article
SR Electronic
T1 TP promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 386706
DO 10.1101/386706
A1 Qiang Zhang
A1 Yuan Qin
A1 Jianmin Zhao
A1 Yuanhao Tang
A1 Xuejiao Hu
A1 Weilong Zhong
A1 Mimi Li
A1 Shumin Zong
A1 Meng Li
A1 Honglian Tao
A1 Zhen Zhang
A1 Shuang Chen
A1 Huijuan Liu
A1 Lan Yang
A1 Honggang Zhou
A1 Yanrong Liu
A1 Tao Sun
A1 Cheng Yang
YR 2018
UL http://biorxiv.org/content/early/2018/08/07/386706.abstract
AB Tumor progression is dependent on metabolic reprogramming. Metastasis and vasculogenic mimicry (VM) are typical tumor progression. The relationship of metastasis, VM and metabolic reprogramming is not clear. In this study, we identified the novel role of Twist1, a VM regulator, in the transcriptional regulation of the expression of thymidine phosphorylase (TP). We demonstrated that TP promoted extracellular thymidine metabolization into ATP and amino acids through pentose Warburg effect by coupling the pentose phosphate pathway and glycolysis. Moreover, Twist1 relied on TP-induced metabolic reprogramming to promote hepatocellular carcinoma (HCC) metastasis and VM formation mediated by VE-Cad, VEGFR1, and VEGFR2 in vitro and in vivo. TP inhibitor tipiracil reduced promotion effect of TP enzyme activity on HCC VM formation and metastasis. Our findings demonstrate that TP, transcriptionally activated by Twist1, promotes HCC VM formation and metastasis through pentose Warburg effect, contributing to tumor progression.