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UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis

Author

Listed:
  • Xiongjun Wang

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences
    Guangzhou University)

  • Ruilong Liu

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Wencheng Zhu

    (University of the Chinese Academy of Sciences)

  • Huiying Chu

    (Dalian Institute of Chemical Physics, Chinese Academy of Sciences)

  • Hua Yu

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Ping Wei

    (Fudan University Shanghai Cancer Center)

  • Xueyuan Wu

    (First Affiliated Hospital of Wenzhou Medical College)

  • Hongwen Zhu

    (Chinese Academy of Sciences)

  • Hong Gao

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Ji Liang

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Guohui Li

    (Dalian Institute of Chemical Physics, Chinese Academy of Sciences)

  • Weiwei Yang

    (University of the Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

Abstract

Cancer metastasis is the primary cause of morbidity and mortality, and accounts for up to 95% of cancer-related deaths1. Cancer cells often reprogram their metabolism to efficiently support cell proliferation and survival2,3. 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 acid4. 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.

Suggested Citation

  • Xiongjun Wang & Ruilong Liu & Wencheng Zhu & Huiying Chu & Hua Yu & Ping Wei & Xueyuan Wu & Hongwen Zhu & Hong Gao & Ji Liang & Guohui Li & Weiwei Yang, 2019. "UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis," Nature, Nature, vol. 571(7763), pages 127-131, July.
    • Handle: RePEc:nat:nature:v:571:y:2019:i:7763:d:10.1038_s41586-019-1340-y
    DOI: 10.1038/s41586-019-1340-y
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    Cited by:

    1. Tao Zhang & Na Zhang & Jing Xing & Shuhua Zhang & Yulu Chen & Daichao Xu & Jinyang Gu, 2023. "UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Jiang Zhu & Kang Chen & Yu H. Sun & Wen Ye & Juntao Liu & Dandan Zhang & Nan Su & Li Wu & Xiaochen Kou & Yanhong Zhao & Hong Wang & Shaorong Gao & Lan Kang, 2023. "LSM1-mediated Major Satellite RNA decay is required for nonequilibrium histone H3.3 incorporation into parental pronuclei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Weiqiang Lu & Jiayan Cui & Wanyan Wang & Qian Hu & Yun Xue & Xi Liu & Ting Gong & Yiping Lu & Hui Ma & Xinyu Yang & Bo Feng & Qi Wang & Naixia Zhang & Yechun Xu & Mingyao Liu & Ruth Nussinov & Feixion, 2024. "PPIA dictates NRF2 stability to promote lung cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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