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

Tongzheng Liu, Jia Yu, Min Deng, Yujiao Yin, Haoxing Zhang, Kuntian Luo, Bo Qin, Yunhui Li, Chenming Wu, Tao Ren, Yang Han, Peng Yin, Jung Jin Kim, Seung Baek Lee, Jing Lin, Lizhi Zhang, Jun Zhang, Somaira Nowsheen, Liewei Wang, Judy BougheyMatthew P. Goetz, Jian Yuan, Zhenkun Lou

Research output: Contribution to journalArticle

52 Scopus citations

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.

Original languageEnglish (US)
Article number13923
JournalNature communications
Volume8
DOIs
StatePublished - Jan 9 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Liu, T., Yu, J., Deng, M., Yin, Y., Zhang, H., Luo, K., Qin, B., Li, Y., Wu, C., Ren, T., Han, Y., Yin, P., Kim, J. J., Lee, S. B., Lin, J., Zhang, L., Zhang, J., Nowsheen, S., Wang, L., ... Lou, Z. (2017). CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1. Nature communications, 8, [13923]. https://doi.org/10.1038/ncomms13923