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Oncometabolite L‐2‐hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma
Author(s) -
Wang Huan,
Wang Liya,
Zheng Qiming,
Lu Zeyi,
Chen Yuanlei,
Shen Danyang,
Xue Dingwei,
Jiang Minxiao,
Ding Lifeng,
Zhang Jie,
Wu Haiyang,
Xia Liqun,
Qian Jun,
Li Gonghui,
Lu Jieyang
Publication year - 2021
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33435
Subject(s) - vasculogenic mimicry , renal cell carcinoma , cancer research , clear cell renal cell carcinoma , demethylation , epigenetics , chemistry , cancer , lung cancer , biology , cell , dna methylation , microbiology and biotechnology , pathology , biochemistry , medicine , metastasis , gene expression , gene , genetics
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 to 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.