Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis

被引：42

作者：

Chen, Xi ^{[1
,2
]}

Cao, Xinwei ^{[1
,2
]}

Sun, Xiaohua ^{[1
,2
]}

Lei, Rong ^{[1
,2
]}

Chen, Pengfei ^{[1
,2
]}

Zhao, Yongxu ^{[1
,2
]}

Jiang, Yuhang ^{[1
,2
]}

Yin, Jie ^{[1
,2
]}

Chen, Ran ^{[1
,2
]}

Ye, Deji ^{[1
,2
]}

Wang, Qi ^{[1
,2
]}

Liu, Zhanjie ^{[1
,2
]}

Liu, Sanhong ^{[1
,2
]}

Cheng, Chunyan ^{[1
,2
]}

Mao, Jie ^{[1
,2
]}

Hou, Yingyong ^{[3
]}

Wang, Mingliang ^{[4
]}

Siebenlist, Ulrich ^{[5
]}

Chin, Y. Eugene ^{[1
,2
,6
]}

Wang, Ying ^{[1
,2
]}

Cao, Liu ^{[7
,8
]}

Hu, Guohong ^{[1
,2
]}

Zhang, Xiaoren ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med SJTUSM, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China

[2] Chinese Acad Sci, SIBS, Shanghai 200025, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Dept Pathol, Sch Med, Shanghai 200032, Peoples R China

[4] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China

[5] NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[6] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Sch Med, Shanghai 200240, Peoples R China

[7] Liaoning Prov Collaborat Innovat Ctr Aging Relate, Shenyang 110001, Peoples R China

[8] China Med Univ, Key Iaboratory Med Cell Biol, Shenyang 110001, Peoples R China

来源：

CELL DEATH & DISEASE | 2016年 / 7卷

基金：

中国国家自然科学基金;

关键词：

GROWTH-FACTOR-BETA; CANDIDATE PROTOONCOGENE BCL-3; FAMILY-MEMBER BCL-3; ONCOPROTEIN BCL-3; ROLES; DEGRADATION; CELLS; GENES; CYLD;

D O I：

10.1038/cddis.2016.405

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Transforming growth factor beta (TGF beta) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the I kappa B family, serves as a critical regulator in TGF beta signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGF beta signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGF beta treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.

引用

页码：e2508 / e2508

页数：12

共 47 条

[1] Regulation of the transforming growth factor β pathway by reversible ubiquitylation [J].