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 M Wang, Judy C BougheyMatthew Philip Goetz, Jian Yuan, Zhenkun Lou

Research output: Contribution to journalArticle

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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

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metastasis
Tumors
breast
cancer
Chemical activation
activation
Neoplasm Metastasis
tumors
Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Epithelial-Mesenchymal Transition
Growth
death
organs
Cells
causes

ASJC Scopus subject areas

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

Cite this

CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1. / Liu, Tongzheng; Yu, Jia; Deng, Min; Yin, Yujiao; Zhang, Haoxing; Luo, Kuntian; Qin, Bo; Li, Yunhui; Wu, Chenming; Ren, Tao; Han, Yang; Yin, Peng; Kim, Jung Jin; Lee, Seung Baek; Lin, Jing; Zhang, Lizhi; Zhang, Jun; Nowsheen, Somaira; Wang, Liewei M; Boughey, Judy C; Goetz, Matthew Philip; Yuan, Jian; Lou, Zhenkun.

In: Nature Communications, Vol. 8, 13923, 09.01.2017.

Research output: Contribution to journalArticle

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, JJ, Lee, SB, Lin, J, Zhang, L, Zhang, J, Nowsheen, S, Wang, LM, Boughey, JC, Goetz, MP, Yuan, J & Lou, Z 2017, 'CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1', Nature Communications, vol. 8, 13923. https://doi.org/10.1038/ncomms13923
Liu, Tongzheng ; Yu, Jia ; Deng, Min ; Yin, Yujiao ; Zhang, Haoxing ; Luo, Kuntian ; Qin, Bo ; Li, Yunhui ; Wu, Chenming ; Ren, Tao ; Han, Yang ; Yin, Peng ; Kim, Jung Jin ; Lee, Seung Baek ; Lin, Jing ; Zhang, Lizhi ; Zhang, Jun ; Nowsheen, Somaira ; Wang, Liewei M ; Boughey, Judy C ; Goetz, Matthew Philip ; Yuan, Jian ; Lou, Zhenkun. / CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1. In: Nature Communications. 2017 ; Vol. 8.
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AU - Kim, Jung Jin

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AU - Zhang, Lizhi

AU - Zhang, Jun

AU - Nowsheen, Somaira

AU - Wang, Liewei M

AU - Boughey, Judy C

AU - Goetz, Matthew Philip

AU - Yuan, Jian

AU - Lou, Zhenkun

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