کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2196054 1550894 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth
چکیده انگلیسی


• Insulin-like growth factor-I (IGF-I) transcriptionally increased Twist1 levels as well as clusterin (CLU) expression.
• At transcriptional level, Twist1 regulated CLU expression and mediated CLU induction by IGF-I.
• As upstream pathway of Twist1, STAT3 mediated Twist1/CLU induction by IGF-I.
• Twist1 and CLU expressions were suggested to be lower in IGF-I-deficient mice.
• Both Twist1 and CLU knockdown suppressed prostate cancer cell proliferation promoted by IGF-I.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 384, Issues 1–2, 25 March 2014, Pages 117–125
نویسندگان
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