中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis

文献类型:期刊论文

作者Wang, Xiongjun2,3,4; Liu, Ruilong2,3; Zhu, Wencheng2; Chu, Huiying5; Yu, Hua2,3; Wei, Ping6; Wu, Xueyuan1; Zhu, Hongwen7; Gao, Hong2,3; Liang, Ji2,3
刊名NATURE
出版日期2019-07-04
卷号571期号:7763页码:127-+
ISSN号0028-0836
DOI10.1038/s41586-019-1340-y
通讯作者Li, Guohui(ghli@dicp.ac.cn) ; Yang, Weiwei(wyang@sibcb.ac.cn)
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.
WOS关键词MOLECULAR-DYNAMICS ; BINDING PROTEIN ; MESENCHYMAL TRANSITION ; HUR ; PHOSPHORYLATION ; DEHYDROGENASE ; NUCLEOTIDE ; SURVIVAL ; GROWTH ; MOUSE
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000473755200043
源URL[http://cas-ir.dicp.ac.cn/handle/321008/175274]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Li, Guohui; Yang, Weiwei
作者单位1.Wenzhou Med Coll, Affiliated Hosp 1, Dept Radiat Oncol, Wenzhou, Peoples R China
2.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
3.Univ Chinese Acad Sci, Shanghai Key Lab Mol Androl, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, Shanghai, Peoples R China
4.Guangzhou Univ, Sch Life Sci, Precise Genome Engn Ctr, Guangzhou, Guangdong, Peoples R China
5.Chinese Acad Sci, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Dalian, Peoples R China
6.Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, 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.,Chu, Huiying.,Yu, Hua.,...&Yang, Weiwei.(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-+.

入库方式: OAI收割

来源:大连化学物理研究所

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