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CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1

Author

Listed:
  • Tongzheng Liu

    (Jinan University Institute of Tumor Pharmacology
    Mayo Clinic)

  • Jia Yu

    (Mayo Clinic)

  • Min Deng

    (Mayo Clinic)

  • Yujiao Yin

    (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine)

  • Haoxing Zhang

    (School of Life Sciences, Southwest University)

  • Kuntian Luo

    (Mayo Clinic
    Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine)

  • Bo Qin

    (Mayo Clinic)

  • Yunhui Li

    (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine)

  • Chenming Wu

    (Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine)

  • Tao Ren

    (East Hospital, Tongji University School of Medicine)

  • Yang Han

    (East Hospital, Tongji University School of Medicine)

  • Peng Yin

    (Mayo Clinic)

  • JungJin Kim

    (Mayo Clinic)

  • SeungBaek Lee

    (Mayo Clinic)

  • Jing Lin

    (First Affiliated Hospital, Chinese PLA General Hospital)

  • Lizhi Zhang

    (Mayo Clinic)

  • Jun Zhang

    (Mayo Clinic)

  • Somaira Nowsheen

    (Medical Scientist Training Program, Mayo Medical School and Mayo Graduate School, Mayo Clinic)

  • Liewei Wang

    (Mayo Clinic)

  • Judy Boughey

    (Mayo Clinic)

  • Matthew P. Goetz

    (Mayo Clinic
    Mayo Clinic)

  • Jian Yuan

    (Mayo Clinic
    Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine)

  • Zhenkun Lou

    (Mayo Clinic)

Abstract

Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial–mesenchymal transition and breast cancer metastasis. Overall, our study establishes the CDK4/6–DUB3 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of breast cancer metastasis.

Suggested Citation

  • Tongzheng Liu & Jia Yu & Min Deng & Yujiao Yin & Haoxing Zhang & Kuntian Luo & Bo Qin & Yunhui Li & Chenming Wu & Tao Ren & Yang Han & Peng Yin & JungJin Kim & SeungBaek Lee & Jing Lin & Lizhi Zhang &, 2017. "CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13923
    DOI: 10.1038/ncomms13923
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