Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L-2-hydroxyglurate (L-2HG). L-2HG has been reported to inhibit the activity of some α-ketoglutarate dependent dioxygenases such as TET enzymes which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L-2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L-2HG was significantly elevated in tumor tissues compared with adjacent tissues. Furthermore, we demonstrated that L-2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L-2HG-induced VM formation. In conclusion, these findings highlighted the pathogenic link between L-2HG and VM and suggested a novel therapeutic target for RCC. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
About The Expert
Huan Wang
Liya Wang
Qiming Zheng
Zeyi Lu
Yuanlei Chen
Danyang Shen
Dingwei Xue
Minxiao Jiang
Lifeng Ding
Jie Zhang
Haiyang Wu
Liqun Xia
Jun Qian
Gonghui Li
Jieyang Lu
References
PubMed