STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion

Kyung Hwa Cho; Kang Jin Jeong; Shang Cheul Shin; Jaeku Kang; Chang Gyo Park; Hoi Young Lee

doi:10.1016/j.canlet.2013.04.024

STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion

Kyung Hwa Cho
, Kang Jin Jeong
, Shang Cheul Shin
, Jaeku Kang
, Chang Gyo Park
, Hoi Young Lee

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

96 Scopus citations

Abstract

TGF-β1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-β1-induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-β1 stimulated STAT3 phosphorylation and HIF-1α expression. Silencing either STAT3 or HIF-1α efficiently attenuated TGF-β1-induced TWIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-β1-induced TWIST1 expression. In addition, STAT3 and HIF-1α up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-β1-induced TWIST1 expression through HIF-1α stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-β1 up-regulating STAT3 activation and HIF-1α stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.

Original language	English (US)
Pages (from-to)	167-173
Number of pages	7
Journal	Cancer Letters
Volume	336
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2013.04.024
State	Published - Aug 9 2013
Externally published	Yes

Funding

We thank Professor Ju-Seog Lee and Gordon B. Mills for invaluable discussion, Mien-Chie Hung for a plasmid-containing TWIST1 promoter. This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (121182) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0015761).

Funders	Funder number
Ministry of Health and Welfare	121182
National Research Foundation of Korea
Ministry of Education, Science and Technology	2011-0015761

Keywords

HIF-1α
Prostate cancer cell invasion
STAT3
TGF-β1
TWIST1

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2013.04.024

Cite this

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title = "STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion",

abstract = "TGF-β1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-β1-induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-β1 stimulated STAT3 phosphorylation and HIF-1α expression. Silencing either STAT3 or HIF-1α efficiently attenuated TGF-β1-induced TWIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-β1-induced TWIST1 expression. In addition, STAT3 and HIF-1α up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-β1-induced TWIST1 expression through HIF-1α stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-β1 up-regulating STAT3 activation and HIF-1α stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.",

keywords = "HIF-1α, Prostate cancer cell invasion, STAT3, TGF-β1, TWIST1",

author = "Cho, \{Kyung Hwa\} and Jeong, \{Kang Jin\} and Shin, \{Shang Cheul\} and Jaeku Kang and Park, \{Chang Gyo\} and Lee, \{Hoi Young\}",

note = "Funding Information: We thank Professor Ju-Seog Lee and Gordon B. Mills for invaluable discussion, Mien-Chie Hung for a plasmid-containing TWIST1 promoter. This study was supported by a grant from the National R\&D Program for Cancer Control, Ministry of Health \& Welfare, Republic of Korea (121182) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0015761). ",

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doi = "10.1016/j.canlet.2013.04.024",

language = "English (US)",

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journal = "Cancer Letters",

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AU - Cho, Kyung Hwa

AU - Jeong, Kang Jin

AU - Shin, Shang Cheul

AU - Kang, Jaeku

AU - Park, Chang Gyo

AU - Lee, Hoi Young

N1 - Funding Information: We thank Professor Ju-Seog Lee and Gordon B. Mills for invaluable discussion, Mien-Chie Hung for a plasmid-containing TWIST1 promoter. This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (121182) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0015761).

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N2 - TGF-β1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-β1-induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-β1 stimulated STAT3 phosphorylation and HIF-1α expression. Silencing either STAT3 or HIF-1α efficiently attenuated TGF-β1-induced TWIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-β1-induced TWIST1 expression. In addition, STAT3 and HIF-1α up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-β1-induced TWIST1 expression through HIF-1α stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-β1 up-regulating STAT3 activation and HIF-1α stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.

AB - TGF-β1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-β1-induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-β1 stimulated STAT3 phosphorylation and HIF-1α expression. Silencing either STAT3 or HIF-1α efficiently attenuated TGF-β1-induced TWIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-β1-induced TWIST1 expression. In addition, STAT3 and HIF-1α up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-β1-induced TWIST1 expression through HIF-1α stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-β1 up-regulating STAT3 activation and HIF-1α stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.

KW - HIF-1α

KW - Prostate cancer cell invasion

KW - STAT3

KW - TGF-β1

KW - TWIST1

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STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion

Abstract

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Keywords

ASJC Scopus subject areas

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