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 Boughey; Matthew P. Goetz; Jian Yuan; Zhenkun Lou

doi:10.1038/ncomms13923

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 journal › Article › peer-review

73 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 language	English (US)
Article number	13923
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms13923
State	Published - Jan 9 2017

ASJC Scopus subject areas

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

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@article{47526ae0da4c4ba18a5f9f62a1d6d921,

title = "CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1",

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.",

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

note = "Funding Information: This work was supported by the National Basic Research Program of China (973 Program, grant no. 2013CB530700), National Natural Science Foundation of China (31270806, 81322031, 81572770 and 31371367), Mayo Clinic Breast Cancer SPORE (P50CA116201) and National Institutes of Health grants (CA203971, CA130996, CA189666 and CA203561). Breast Cancer Genome-Guided Therapy study (BEAUTY) was supported by Center for Individualized Medicine of Mayo Clinic. Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

month = jan,

day = "9",

doi = "10.1038/ncomms13923",

language = "English (US)",

volume = "8",

journal = "Nature communications",

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T1 - CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1

AU - Liu, Tongzheng

AU - Yu, Jia

AU - Deng, Min

AU - Yin, Yujiao

AU - Zhang, Haoxing

AU - Luo, Kuntian

AU - Qin, Bo

AU - Li, Yunhui

AU - Wu, Chenming

AU - Ren, Tao

AU - Han, Yang

AU - Yin, Peng

AU - Kim, Jung Jin

AU - Lee, Seung Baek

AU - Lin, Jing

AU - Zhang, Lizhi

AU - Zhang, Jun

AU - Nowsheen, Somaira

AU - Wang, Liewei

AU - Boughey, Judy

AU - Goetz, Matthew P.

AU - Yuan, Jian

AU - Lou, Zhenkun

N1 - Funding Information: This work was supported by the National Basic Research Program of China (973 Program, grant no. 2013CB530700), National Natural Science Foundation of China (31270806, 81322031, 81572770 and 31371367), Mayo Clinic Breast Cancer SPORE (P50CA116201) and National Institutes of Health grants (CA203971, CA130996, CA189666 and CA203561). Breast Cancer Genome-Guided Therapy study (BEAUTY) was supported by Center for Individualized Medicine of Mayo Clinic. Publisher Copyright: © The Author(s) 2017.

PY - 2017/1/9

Y1 - 2017/1/9

N2 - 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.

AB - 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.

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

Abstract

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