Opposing roles of TGFβ and BMP signaling in prostate cancer development

被引：32

作者：

Lu, Xin ^{[1
,2
,3
]}

Jin, Eun-Jung ^{[1
,4
]}

Cheng, Xi ^{[2
,5
]}

Feng, Shan ^{[2
,6
]}

Shang, Xiaoying ^{[1
]}

Deng, Pingna ^{[1
]}

Jiang, Shan ^{[7
]}

Chang, Qing ^{[7
]}

Rahmy, Sharif ^{[2
]}

Chaudhary, Seema ^{[2
]}

Lu, Xuemin ^{[2
]}

Zhao, Ren ^{[5
]}

Wang, Y. Alan ^{[1
]}

DePinho, Ronald A. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77054 USA

[2] Univ Notre Dame, Dept Biol Sci, Boler Parseghian Ctr Rare & Neglected Dis, Harper Canc Res Inst, Notre Dame, IN 46556 USA

[3] Indiana Univ, Melvin & Bren Simon Canc Ctr, Tumor Microenvironm & Metastasis Program, Indianapolis, IN 46202 USA

[4] Wonkwang Univ, Dept Biol Sci, Iksan 570749, South Korea

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

[6] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

[7] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77054 USA

来源：

GENES & DEVELOPMENT | 2017年 / 31卷 / 23-24期

基金：

美国国家卫生研究院;

关键词：

PTEN; SMAD4; TGFBR2; BMPR2; prostate cancer; bone metastasis; MORPHOGENETIC PROTEIN-7; BONE; PROGRESSION; RECEPTOR; CELLS; DIFFERENTIATION; INFLAMMATION; SUPPRESSION; METASTASIS; EXPRESSION;

D O I：

10.1101/gad.307116.117

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor beta (TGF beta) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGF beta receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing itspromoting role in BMP6-driven prostate cancer progression. These analyses reveal the complexity ofTGF beta-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.

引用

页码：2337 / 2342

页数：6

共 39 条

[1] The Molecular Taxonomy of Primary Prostate Cancer [J].

Abeshouse, Adam ;

Ahn, Jaeil ;

Akbani, Rehan ;

Ally, Adrian ;

Amin, Samirkumar ;

Andry, Christopher D. ;

Annala, Matti ;

Aprikian, Armen ;

Armenia, Joshua ;

Arora, Arshi ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barbieri, Christopher E. ;

Bauer, Thomas ;

Benz, Christopher C. ;

Bergeron, Alain ;

Beroukhim, Rameen ;

Berrios, Mario ;

Bivol, Adrian ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

dos Reis, Rodolfo Borges ;

Boutros, Paul C. ;

Bowen, Jay ;

Bowlby, Reanne ;

Boyd, Jeffrey ;

Bradley, Robert K. ;

Breggia, Anne ;

Brimo, Fadi ;

Bristow, Christopher A. ;

Brooks, Denise ;

Broom, Bradley M. ;

Bryce, Alan H. ;

Bubley, Glenn ;

Burks, Eric ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Canes, David ;

Carlotti, Carlos G. ;

Carlsen, Rebecca ;

Carmel, Michel ;

Carroll, Peter R. ;

Carter, Scott L. ;

Cartun, Richard ;

Carver, Brett S. ;

Chan, June M. ;

Chang, Matthew T. ;

Chen, Yu .

CELL, 2015, 163 (04) :1011-1025

[2]

Barnes J, 1995, WORLD J UROL, V13, P337

[3] Generation of a floxed allele of the mouse BMP type II receptor gene [J].

Beppu, H ;

Lei, H ;

Bloch, KD ;

Li, E .

GENESIS, 2005, 41 (03) :133-137

[4] Activation of Akt signaling in prostate induces a TGFβ-mediated restraint on cancer progression and metastasis [J].

Bjerke, G. A. ;

Yang, C-S ;

Frierson, H. F. ;

Paschal, B. M. ;

Wotton, D. .

ONCOGENE, 2014, 33 (28) :3660-3667

[5] p38 MAP kinase mediates apoptosis through phosphorylation of BimEL at Ser-65 [J].

Cai, Beibei ;

Chang, Sandra H. ;

Becker, Esther B. E. ;

Bonni, Azad ;

Xia, Zhengui .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (35) :25215-25222

[6] Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis [J].

Chen, ZB ;

Trotman, LC ;

Shaffer, D ;

Lin, HK ;

Dotan, ZA ;

Niki, M ;

Koutcher, JA ;

Scher, HI ;

Ludwig, T ;

Gerald, W ;

Cordon-Cardo, C ;

Pandolfi, PP .

NATURE, 2005, 436 (7051) :725-730

[7] Single luminal epithelial progenitors can generate prostate organoids in culture [J].

Chua, Chee Wai ;

Shibata, Maho ;

Lei, Ming ;

Toivanen, Roxanne ;

Barlow, LaMont J. ;

Bergren, Sarah K. ;

Badani, Ketan K. ;

Mc Kiernan, James M. ;

Benson, Mitchell C. ;

Hibshoosh, Hanina ;

Shen, Michael M. .

NATURE CELL BIOLOGY, 2014, 16 (10) :951-961

[8] Conditional inactivation of the TGF-β type II receptor using Cre:Lox [J].

Chytil, A ;

Magnuson, MA ;

Wright, CVE ;

Moses, HL .

GENESIS, 2002, 32 (02) :73-75

[9] BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype [J].

Darby, S. ;

Cross, S. S. ;

Brown, N. J. ;

Hamdy, F. C. ;

Robson, C. N. .

JOURNAL OF PATHOLOGY, 2008, 214 (03) :394-404

[10] Telomerase Reactivation following Telomere Dysfunction Yields Murine Prostate Tumors with Bone Metastases [J].

Ding, Zhihu ;

Wu, Chang-Jiun ;

Jaskelioff, Mariela ;

Ivanova, Elena ;

Kost-Alimova, Maria ;

Protopopov, Alexei ;

Chu, Gerald C. ;

Wang, Guocan ;

Lu, Xin ;

Labrot, Emma S. ;

Hu, Jian ;

Wang, Wei ;

Xiao, Yonghong ;

Zhang, Hailei ;

Zhang, Jianhua ;

Zhang, Jingfang ;

Gan, Boyi ;

Perry, Samuel R. ;

Jiang, Shan ;

Li, Liren ;

Horner, James W. ;

Wang, Y. Alan ;

Chin, Lynda ;

DePinho, Ronald A. .

CELL, 2012, 148 (05) :896-907

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