Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth

Ario Takeuchi, Masaki Shiota, Eliana Beraldi, Daksh Thaper, Kiyoshi Takahara, Naokazu Ibuki, Michael Pollak, Michael E. Cox, Seiji Naito, Martin E. Gleave, Amina Zoubeidi

研究成果: Article

8 引用 (Scopus)

抄録

Clusterin (CLU) is cytoprotective molecular chaperone that is highly expressed in castrate-resistant prostate cancer (CRPC). CRPC is also characterized by increased insulin-like growth factor (IGF)-I responsiveness which induces prostate cancer survival and CLU expression. However, how IGF-I induces CLU expression and whether CLU is required for IGF-mediated growth signaling remain unknown. Here we show that IGF-I induced CLU via STAT3-Twist1 signaling pathway. In response to IGF-I, STAT3 was phosphorylated, translocated to the nucleus and bound to the Twist1 promoter to activate Twist1 transcription. In turn, Twist1 bound to E-boxes on the CLU promoter and activated CLU transcription. Inversely, we demonstrated that knocking down Twist1 abrogated IGF-I induced CLU expression, indicating that Twist1 mediated IGF-I-induced CLU expression. When PTEN knockout mice were crossed with lit/. lit mice, the resultant IGF-I deficiency suppressed Twist1 as well as CLU gene expression in mouse prostate glands. Moreover, both Twist1 and CLU knockdown suppressed prostate cancer growth accelerated by IGF-I, suggesting the relevance of this signaling not only in an in vitro, but also in an in vivo. Collectively, this study indicates that IGF-I induces CLU expression through sequential activation of STAT3 and Twist1, and suggests that this signaling cascade plays a critical role in prostate cancer pathogenesis.

元の言語English
ページ(範囲)117-125
ページ数9
ジャーナルMolecular and Cellular Endocrinology
384
発行部数1-2
DOI
出版物ステータスPublished - 25-03-2014

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Clusterin
Insulin-Like Growth Factor I
Prostatic Neoplasms
Growth
Transcription
Molecular Chaperones
Somatomedins
Gene expression
Knockout Mice
Prostate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

これを引用

Takeuchi, Ario ; Shiota, Masaki ; Beraldi, Eliana ; Thaper, Daksh ; Takahara, Kiyoshi ; Ibuki, Naokazu ; Pollak, Michael ; Cox, Michael E. ; Naito, Seiji ; Gleave, Martin E. ; Zoubeidi, Amina. / Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth. :: Molecular and Cellular Endocrinology. 2014 ; 巻 384, 番号 1-2. pp. 117-125.
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abstract = "Clusterin (CLU) is cytoprotective molecular chaperone that is highly expressed in castrate-resistant prostate cancer (CRPC). CRPC is also characterized by increased insulin-like growth factor (IGF)-I responsiveness which induces prostate cancer survival and CLU expression. However, how IGF-I induces CLU expression and whether CLU is required for IGF-mediated growth signaling remain unknown. Here we show that IGF-I induced CLU via STAT3-Twist1 signaling pathway. In response to IGF-I, STAT3 was phosphorylated, translocated to the nucleus and bound to the Twist1 promoter to activate Twist1 transcription. In turn, Twist1 bound to E-boxes on the CLU promoter and activated CLU transcription. Inversely, we demonstrated that knocking down Twist1 abrogated IGF-I induced CLU expression, indicating that Twist1 mediated IGF-I-induced CLU expression. When PTEN knockout mice were crossed with lit/. lit mice, the resultant IGF-I deficiency suppressed Twist1 as well as CLU gene expression in mouse prostate glands. Moreover, both Twist1 and CLU knockdown suppressed prostate cancer growth accelerated by IGF-I, suggesting the relevance of this signaling not only in an in vitro, but also in an in vivo. Collectively, this study indicates that IGF-I induces CLU expression through sequential activation of STAT3 and Twist1, and suggests that this signaling cascade plays a critical role in prostate cancer pathogenesis.",
author = "Ario Takeuchi and Masaki Shiota and Eliana Beraldi and Daksh Thaper and Kiyoshi Takahara and Naokazu Ibuki and Michael Pollak and Cox, {Michael E.} and Seiji Naito and Gleave, {Martin E.} and Amina Zoubeidi",
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Takeuchi, A, Shiota, M, Beraldi, E, Thaper, D, Takahara, K, Ibuki, N, Pollak, M, Cox, ME, Naito, S, Gleave, ME & Zoubeidi, A 2014, 'Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth', Molecular and Cellular Endocrinology, 巻. 384, 番号 1-2, pp. 117-125. https://doi.org/10.1016/j.mce.2014.01.012

Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth. / Takeuchi, Ario; Shiota, Masaki; Beraldi, Eliana; Thaper, Daksh; Takahara, Kiyoshi; Ibuki, Naokazu; Pollak, Michael; Cox, Michael E.; Naito, Seiji; Gleave, Martin E.; Zoubeidi, Amina.

:: Molecular and Cellular Endocrinology, 巻 384, 番号 1-2, 25.03.2014, p. 117-125.

研究成果: Article

TY - JOUR

T1 - Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth

AU - Takeuchi, Ario

AU - Shiota, Masaki

AU - Beraldi, Eliana

AU - Thaper, Daksh

AU - Takahara, Kiyoshi

AU - Ibuki, Naokazu

AU - Pollak, Michael

AU - Cox, Michael E.

AU - Naito, Seiji

AU - Gleave, Martin E.

AU - Zoubeidi, Amina

PY - 2014/3/25

Y1 - 2014/3/25

N2 - Clusterin (CLU) is cytoprotective molecular chaperone that is highly expressed in castrate-resistant prostate cancer (CRPC). CRPC is also characterized by increased insulin-like growth factor (IGF)-I responsiveness which induces prostate cancer survival and CLU expression. However, how IGF-I induces CLU expression and whether CLU is required for IGF-mediated growth signaling remain unknown. Here we show that IGF-I induced CLU via STAT3-Twist1 signaling pathway. In response to IGF-I, STAT3 was phosphorylated, translocated to the nucleus and bound to the Twist1 promoter to activate Twist1 transcription. In turn, Twist1 bound to E-boxes on the CLU promoter and activated CLU transcription. Inversely, we demonstrated that knocking down Twist1 abrogated IGF-I induced CLU expression, indicating that Twist1 mediated IGF-I-induced CLU expression. When PTEN knockout mice were crossed with lit/. lit mice, the resultant IGF-I deficiency suppressed Twist1 as well as CLU gene expression in mouse prostate glands. Moreover, both Twist1 and CLU knockdown suppressed prostate cancer growth accelerated by IGF-I, suggesting the relevance of this signaling not only in an in vitro, but also in an in vivo. Collectively, this study indicates that IGF-I induces CLU expression through sequential activation of STAT3 and Twist1, and suggests that this signaling cascade plays a critical role in prostate cancer pathogenesis.

AB - Clusterin (CLU) is cytoprotective molecular chaperone that is highly expressed in castrate-resistant prostate cancer (CRPC). CRPC is also characterized by increased insulin-like growth factor (IGF)-I responsiveness which induces prostate cancer survival and CLU expression. However, how IGF-I induces CLU expression and whether CLU is required for IGF-mediated growth signaling remain unknown. Here we show that IGF-I induced CLU via STAT3-Twist1 signaling pathway. In response to IGF-I, STAT3 was phosphorylated, translocated to the nucleus and bound to the Twist1 promoter to activate Twist1 transcription. In turn, Twist1 bound to E-boxes on the CLU promoter and activated CLU transcription. Inversely, we demonstrated that knocking down Twist1 abrogated IGF-I induced CLU expression, indicating that Twist1 mediated IGF-I-induced CLU expression. When PTEN knockout mice were crossed with lit/. lit mice, the resultant IGF-I deficiency suppressed Twist1 as well as CLU gene expression in mouse prostate glands. Moreover, both Twist1 and CLU knockdown suppressed prostate cancer growth accelerated by IGF-I, suggesting the relevance of this signaling not only in an in vitro, but also in an in vivo. Collectively, this study indicates that IGF-I induces CLU expression through sequential activation of STAT3 and Twist1, and suggests that this signaling cascade plays a critical role in prostate cancer pathogenesis.

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