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

被引：125

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：

美国国家卫生研究院; 中国国家自然科学基金;

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

共 60 条

[1] EMT: 2016
Angela Nieto, M.
Huang, Ruby Yun-Ju
Jackson, Rebecca A.
Thiery, Jean Paul
[J]. CELL, 2016, 166 (01) : 21 - 45
[2] The history and future of targeting cyclin-dependent kinases in cancer therapy
Asghar, Uzma
Witkiewicz, Agnieszka K.
Turner, Nicholas C.
Knudsen, Erik S.
[J]. NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (02) : 130 - 146
[3] Metastatic cancer cell
Bacac, Marina
Stamenkovic, Ivan
[J]. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2008, 3 : 221 - 247
[4] Cytokine-regulated protein degradation by the ubiquitination system
Baek, KH
[J]. CURRENT PROTEIN & PEPTIDE SCIENCE, 2006, 7 (02) : 171 - 177
[5] The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells
Batlle, E
Sancho, E
Franci, C
Domínguez, D
Monfar, M
Baulida, J
de Herreros, AG
[J]. NATURE CELL BIOLOGY, 2000, 2 (02) : 84 - 89
[6] FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Beaver, Julia A.
Amiri-Kordestani, Laleh
Charlab, Rosane
Chen, Wei
Palmby, Todd
Tilley, Amy
Zirkelbach, Jeanne Fourie
Yu, Jingyu
Liu, Qi
Zhao, Liang
Crich, Joyce
Chen, Xiao Hong
Hughes, Minerva
Bloomquist, Erik
Tang, Shenghui
Sridhara, Rajeshwari
Kluetz, Paul G.
Kim, Geoffrey
Ibrahim, Amna
Pazdur, Richard
Cortazar, Patricia
[J]. CLINICAL CANCER RESEARCH, 2015, 21 (21) : 4760 - 4766
[7] A pooled analysis of bone marrow micrometastasis in breast cancer
Braun, S
Vogl, FD
Naume, B
Janni, W
Osborne, MP
Coombes, RC
Schlimok, G
Diel, IJ
Gerber, B
Gebauer, G
Pierga, JY
Marth, C
Oruzio, D
Wiedswang, G
Solomayer, EF
Kundt, G
Strobl, B
Fehm, T
Wong, GYC
Bliss, J
Vincent-Salomon, A
Pantel, K
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (08) : 793 - 802
[8] The DUB/USP17 deubiquitinating enzymes, a multigene family within a tandemly repeated sequence
Burrows, JF
McGrattan, MJ
Johnston, JA
[J]. GENOMICS, 2005, 85 (04) : 524 - 529
[9] The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression
Cano, A
Pérez-Moreno, MA
Rodrigo, I
Locascio, A
Blanco, MJ
del Barrio, MG
Portillo, F
Nieto, MA
[J]. NATURE CELL BIOLOGY, 2000, 2 (02) : 76 - 83
[10] How Does Multistep Tumorigenesis Really Proceed?
Chaffer, Christine L.
Weinberg, Robert A.
[J]. CANCER DISCOVERY, 2015, 5 (01) : 22 - 24

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