Opposing roles of TGFβ and BMP signaling in prostate cancer development

Xin Lu; Eun Jung Jin; Xi Cheng; Shan Feng; Xiaoying Shang; Pingna Deng; Shan Jiang; Qing Chang; Sharif Rahmy; Seema Chaudhary; Xuemin Lu; Ren Zhao; Y. Alan Wang; Ronald A. Depinho

doi:10.1101/gad.307116.117

Opposing roles of TGFβ and BMP signaling in prostate cancer development

Xin Lu, Eun Jung Jin, Xi Cheng, Shan Feng, Xiaoying Shang, Pingna Deng, Shan Jiang, Qing Chang, Sharif Rahmy, Seema Chaudhary, Xuemin Lu, Ren Zhao, Y. Alan Wang, Ronald A. Depinho

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. Thesestudies 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 ofTGFβ-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.

Original language	English (US)
Pages (from-to)	2337-2342
Number of pages	6
Journal	Genes and Development
Volume	31
Issue number	23-24
DOIs	https://doi.org/10.1101/gad.307116.117
State	Published - Dec 1 2017

Keywords

BMPR2
Bone Metastasis
PTEN
Prostate cancer
SMAD4
TGFBR2

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.307116.117

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title = "Opposing roles of TGFβ and BMP signaling in prostate cancer development",

abstract = "SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. Thesestudies 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 ofTGFβ-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.",

keywords = "BMPR2, Bone Metastasis, PTEN, Prostate cancer, SMAD4, TGFBR2",

author = "Xin Lu and Jin, {Eun Jung} and Xi Cheng and Shan Feng and Xiaoying Shang and Pingna Deng and Shan Jiang and Qing Chang and Sharif Rahmy and Seema Chaudhary and Xuemin Lu and Ren Zhao and Wang, {Y. Alan} and Depinho, {Ronald A.}",

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year = "2017",

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doi = "10.1101/gad.307116.117",

language = "English (US)",

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AU - Lu, Xin

AU - Jin, Eun Jung

AU - Cheng, Xi

AU - Feng, Shan

AU - Shang, Xiaoying

AU - Deng, Pingna

AU - Jiang, Shan

AU - Chang, Qing

AU - Rahmy, Sharif

AU - Chaudhary, Seema

AU - Lu, Xuemin

AU - Zhao, Ren

AU - Wang, Y. Alan

AU - Depinho, Ronald A.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. Thesestudies 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 ofTGFβ-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.

AB - SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. Thesestudies 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 ofTGFβ-BMPsignaling and illuminate potential therapeutic targets for prostate cancer.

KW - BMPR2

KW - Bone Metastasis

KW - PTEN

KW - Prostate cancer

KW - SMAD4

KW - TGFBR2

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SN - 0890-9369

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EP - 2342

JO - Genes and Development

JF - Genes and Development

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ER -

Opposing roles of TGFβ and BMP signaling in prostate cancer development

Abstract

Keywords

ASJC Scopus subject areas

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