Scientists have discovered metabolic small molecules that inhibit lung cancer metastasis
June 27, 2019 Source: Voice of the Chinese Academy of Sciences
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Lung cancer is the most common malignant tumor in the world and the highest morbidity and mortality in China. The important reason for the high mortality rate is cancer cell metastasis. Traditional surgery and postoperative radiotherapy and chemotherapy can effectively control the primary tumor, but the tumors that are metastatic are often at a loss.
The latest research by Yang Weiwei, a research group of the Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences, found that the cell metabolite, uridine diphosphate glucose, can effectively inhibit lung cancer metastasis and provide new targets and biomarkers for monitoring and blocking lung cancer metastasis. . The result was published online in the early morning of June 27th, Beijing time in the internationally authoritative academic journal Nature.
According to statistics, the number of new cases of lung cancer in China exceeds 730,000, the death toll exceeds 610,000, and the five-year survival rate is as low as 16.1%. Lung cancer has become the "first cancer" and "the number one cancer killer". More than 95% of cancer deaths are caused by cancer cell metastasis. Previous studies have shown that metabolic abnormalities are an important feature of malignant tumors. These abnormal metabolisms can reshape tumor cells to enhance their growth and survival, but little is known about whether and how they support tumor metastasis.
Snail is a protein that promotes rapid cancer metastasis. Normally its mRNA is degraded by a class of "cleavage" enzymes in the cell, and Snail is "hard to protect itself." But when Snail's mRNA binds to another protein called HuR, Snail becomes more stable, making the cleavage enzyme "uninvited." Yang Weiwei’s team found that HuR protein in normal cells is tightly bound to uridine diphosphate glucose. However, in lung cancer cells, tyrosine at position 473 of uridine diphosphate glucose dehydrogenase is highly phosphorylated. Binding to the HuR protein catalyzes the uridine diphosphate glucose, which is originally tightly bound by HuR, to form uridine diphosphate glucuronic acid and "unbundle" the HuR protein. The "unbundled" HuR protein binds to Snail mRNA, which increases the stability of Snail, enhances the migration ability of tumor cells, and promotes lung cancer metastasis.
The researchers conducted in-depth analysis of clinical data and found that the uridine diphosphate glucose content in lung cancer patients is closely related to the metastasis and recurrence of lung cancer. Compared with the primary lesion, the uridine diphosphate glucose content of the lung cancer tissue in the metastatic lesion was drastically reduced; more importantly, the uridine diphosphate glucose content in the blood samples of the lung cancer patients with distant metastasis was also significantly reduced. In addition, they found that the higher the level of tyrosine phosphorylation of uridine diphosphate glucose dehydrogenase in lung cancer tissue, the greater the incidence of lung cancer metastasis, and the worse the prognosis of patients.
This study reveals for the first time the new function of uridine diphosphate glucose inhibition and its mechanism of action, providing the first biochemical marker for the diagnosis of lung cancer metastasis, contributing to the discovery of early metastasis of tumors, and also providing treatment for metastatic lung cancer. A new strategy.
This research was mainly completed by the research team of Yang Weiwei of the Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences and the Li Guohui research group of the Dalian Institute of Chemical Physics. Wang Xiongjun, associate professor of Guangzhou University, Liu Ruilong and Zhu Wencheng, Ph.D. students of the Center for Excellence in Molecular Cell Science, and Chu Huizhen, Dalian Institute of Chemical Physics, are the co-first authors of this article. Researcher Yang Weiwei is the primary correspondent of the paper, and researcher Li Guohui is the co-author of the paper. The work was led by Cheng Hong, a researcher at the Center for Excellence in Molecular Cell Science, and Li Fei, a doctoral student at Gaodong Lab. The research was funded by the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Ministry of Youth. Data collection was supported by the Molecular Platform, Chemical Platform, Animal Platform and GTP Center of the Center for Excellence in Molecular Cell Science Innovation Center.
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