کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525311 1546661 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleAndrogen-deprivation therapy with enzalutamide enhances prostate cancer metastasis via decreasing the EPHB6 suppressor expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleAndrogen-deprivation therapy with enzalutamide enhances prostate cancer metastasis via decreasing the EPHB6 suppressor expression
چکیده انگلیسی


- Loss of EPHB6 expression is associated with poor prognosis in prostate cancer patients.
- Overexpression of EPHB6 decreases PCa invasion in vitro.
- Enz could decrease EPHB6 expression to induce the activation of JNK pathway to increase CRPC cell invasion.

Early studies suggested that using ADT with the recently developed anti-androgen Enzalutamide (Enz, also named as MDV3100 could extent castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months. Yet the therapy in most patients might eventually fail due to development of Enz-resistance. Here we found Enz might also increase some unwanted side-effects via increasing the CRPC cell invasion that might involve altering the Enz-mediated androgen receptor (AR)/EPHB6 suppressor/JNK signaling. Results from multiple clinical surveys also indicated that EPHP6 might function as a suppressor of PCa metastasis. Mechanism dissection revealed that Enz-mediated AR might function via binding to the androgen-response-element (ARE) on the EPHB6 promoter to decrease EPHB6 suppressor expression, which might then activate the phosphorylation of JNK signals to increase the CRPC cell invasion. Targeting this newly identified AR/EPHB6/JNK signaling with JNK inhibitor (SP600125) may then block/reverse the Enz-increased CRPC cell invasion. Collectively, our results suggest that Enz may increase CRPC cell invasion via altering the AR/EPHB6/JNK/MMP9 signaling and targeting this newly identified signaling may help us to increase the Enz efficacy to better suppress the CRPC at the later metastatic stage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 408, 1 November 2017, Pages 155-163
نویسندگان
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