UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis
文献类型：期刊论文
| 作者 | Wang, Xiongjun5,6,7; Liu, Ruilong6,7; Zhu, Wencheng7; Yu, Hua6,7; Gao, Hong6,7; Liang, Ji6,7; Yang, Weiwei6,7; Chu, Huiying4; Li, Guohui4; Wei, Ping3 |
| 刊名 | NATURE
 |
| 出版日期 | 2019 |
| 卷号 | 571期号:7763页码:127-+ |
| ISSN号 | 0028-0836 |
| 关键词 | MOLECULAR-DYNAMICS BINDING PROTEIN MESENCHYMAL TRANSITION HUR PHOSPHORYLATION DEHYDROGENASE NUCLEOTIDE SURVIVAL GROWTH MOUSE |
| DOI | 10.1038/s41586-019-1340-y |
| 文献子类 | Article |
| 英文摘要 | Cancer metastasis is the primary cause of morbidity and mortality, and accounts for up to 95% of cancer-related deaths(1). Cancer cells often reprogram their metabolism to efficiently support cell proliferation and survival(2,3). However, whether and how those metabolic alterations contribute to the migration of tumour cells remain largely unknown. UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in the uronic acid pathway, and converts UDP-glucose to UDP-glucuronic acid(4). Here we show that, after activation of EGFR, UGDH is phosphorylated at tyrosine 473 in human lung cancer cells. Phosphorylated UGDH interacts with Hu antigen R (HuR) and converts UDP-glucose to UDP-glucuronic acid, which attenuates the UDP-glucose-mediated inhibition of the association of HuR with SNAI1 mRNA and therefore enhances the stability of SNAI1 mRNA. Increased production of SNAIL initiates the epithelial-mesenchymal transition, thus promoting the migration of tumour cells and lung cancer metastasis. In addition, phosphorylation of UGDH at tyrosine 473 correlates with metastatic recurrence and poor prognosis of patients with lung cancer. Our findings reveal a tumour-suppressive role of UDP-glucose in lung cancer metastasis and uncover a mechanism by which UGDH promotes tumour metastasis by increasing the stability of SNAI1 mRNA. |
| 学科主题 | Multidisciplinary Sciences |
| 语种 | 英语 |
| WOS记录号 | WOS:000473755200043 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/3570]  |
| 专题 | 生化所2019-2020年发文 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China, 2.Wenzhou Med Coll, Affiliated Hosp 1, Dept Radiat Oncol, Wenzhou, Peoples R China; 3.Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China; 4.Chinese Acad Sci, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Dalian, Peoples R China; 5.Guangzhou Univ, Sch Life Sci, Precise Genome Engn Ctr, Guangzhou, Guangdong, Peoples R China; 6.Univ Chinese Acad Sci, Shanghai Key Lab Mol Androl, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, Shanghai, Peoples R China; 7.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,Chinese Acad Sci, Innovat Ctr Cell Signaling Network,State Key Lab, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Xiongjun,Liu, Ruilong,Zhu, Wencheng,et al. UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis[J]. NATURE,2019,571(7763):127-+. |
| APA | Wang, Xiongjun.,Liu, Ruilong.,Zhu, Wencheng.,Yu, Hua.,Gao, Hong.,...&,.(2019).UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis.NATURE,571(7763),127-+. |
| MLA | Wang, Xiongjun,et al."UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis".NATURE 571.7763(2019):127-+. |
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