کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815309 | 1058467 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
eukaryotic initiation factor 4E binding protein 1Protein Kinase C-δp70 S6 kinaseLRP6mTORC1 signalingPKCδfrizzledFZDmTORC14E-BP1eIF4ECK1GSK3βAMPKTNBCFBSp70S6KAPCTCF/LEF - TCF / LEFadenomatous polyposis coli - آدنوماتوز پولیپوزیس کولی یا آدنوماتوس پولیپوزیس کولای Rottlerin - رتلرینCancer - سرطانTriple negative breast cancer - سرطان سینه سه گانه منفیfetal bovine serum - سرم جنین گاوWnt signaling - سیگنال WntConditioned medium - شرایط محیطیeukaryotic initiation factor 4E - عامل آغاز کننده یوکاریوتی 4E5′-AMP-activated protein Kinase - پروتئین کیناز 5'-AMP فعالcasein kinase 1 - کازئین کیناز 1Drug discovery - کشف مواد مخدرGlycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3β
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells](/preview/png/10815309.png)
چکیده انگلیسی
Activation of Wnt/β-catenin signaling can result in up-regulation of mTORC1 signaling in cancer cells. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling. We found that rottlerin, a natural plant polyphenol, suppressed LRP6 expression and phosphorylation, and inhibited Wnt/β-catenin signaling in HEK293 cells. Furthermore, the inhibitory effects of rottlerin on LRP6 expression/phosphorylation and Wnt/β-catenin signaling were confirmed in human prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, rottlerin promoted LRP6 degradation, but had no effects on LRP6 transcriptional activity. In addition, rottlerin-mediated LRP6 down-regulation was unrelated to activation of 5â²-AMP-activated protein kinase (AMPK). Importantly, we also found that rottlerin inhibited mTORC1 signaling in prostate and breast cancer cells. Finally, we demonstrated that rottlerin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/β-catenin and mTORC1 signaling, in prostate and breast cancer cells, and displayed remarkable anticancer activity with IC50 values between 0.7 and 1.7 μM for prostate cancer PC-3 and DU145 cells and breast cancer MDA-MB-231 and T-47D cells. The IC50 values are comparable to those shown to suppress the activities of Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells. Our data indicate that rottlerin is a novel LRP6 inhibitor and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells, and that LRP6 represents a potential therapeutic target for cancers.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 6, June 2014, Pages 1303-1309
Journal: Cellular Signalling - Volume 26, Issue 6, June 2014, Pages 1303-1309
نویسندگان
Wenyan Lu, Cuihong Lin, Yonghe Li,