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.
International journal of cancer. 2020 Dec 15 [Epub ahead of print]
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
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Department of Urology, the Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine, Hangzhou, China.