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

被引：132

作者：

Liu, Tongzheng ^{[1
,2
]}

Yu, Jia ^{[3
]}

Deng, Min ^{[2
]}

Yin, Yujiao ^{[4
,5
]}

Zhang, Haoxing ^{[6
]}

Luo, Kuntian ^{[2
,4
,5
]}

Qin, Bo ^{[2
]}

Li, Yunhui ^{[4
,5
]}

Wu, Chenming ^{[4
,5
]}

Ren, Tao ^{[7
]}

Han, Yang ^{[8
]}

Yin, Peng ^{[9
]}

Kim, JungJin ^{[2
]}

Lee, SeungBaek ^{[2
]}

Lin, Jing ^{[10
]}

Zhang, Lizhi ^{[11
]}

Zhang, Jun ^{[11
]}

Nowsheen, Somaira ^{[12
,13
]}

Wang, Liewei ^{[3
]}

Boughey, Judy ^{[14
]}

Goetz, Matthew P. ^{[2
,3
]}

Yuan, Jian ^{[2
,4
,5
]}

Lou, Zhenkun ^{[2
]}

机构：

[1] Jinan Univ, Inst Tumor Pharmacol, Guangzhou 510632, Guangdong, Peoples R China

[2] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA

[4] Tongji Univ, Sch Med, East Hosp, Res Ctr Translat Med, Shanghai 200120, Peoples R China

[5] Tongji Univ, Sch Med, East Hosp, Key Lab Arrhythmias,Minist Educ China, Shanghai 200120, Peoples R China

[6] Southwest Univ, Sch Life Sci, Chongqing 400715, Peoples R China

[7] Tongji Univ, Sch Med, East Hosp, Dept Resp Med, Shanghai 200120, Peoples R China

[8] Tongji Univ, Sch Med, East Hosp, Dept Pathol, Shanghai 200120, Peoples R China

[9] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

[10] Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Beijing 100818, Peoples R China

[11] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[12] Mayo Clin, Mayo Med Sch, Med Scientist Training Program, Rochester, MN 55905 USA

[13] Mayo Clin, Mayo Grad Sch, Rochester, MN 55905 USA

[14] Mayo Clin, Div Subspecialty Gen Surg, Rochester, MN 55905 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN BREAST-CANCER; TRANSCRIPTION FACTOR SNAIL; E-CADHERIN REPRESSION; KINASE; 4/6; INHIBITOR; TUMOR-METASTASIS; CELL; PROGRESSION; PHOSPHORYLATION; PLASTICITY;

D O I：

10.1038/ncomms13923

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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