کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509412 | 1400457 | 2016 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Negative control of TRAIL-R1 signaling by transforming growth factor β1 in pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
EGFJnkMFIMcl-1ERKactivin receptor-like kinase 5DISCFADDLexABcl-xLFLIPALK5FLICE-like inhibitory proteinc-Jun N-terminal kinase - C-Jun N-terminal kinaseepidermal growth factor - عامل رشد اپیدرمیB-cell lymphoma-extra large - لنفوم سلول B-فوق العاده بزرگ استMyeloid cell leukemia 1 - لوسمی سلول میلوئید 1death inducing signaling complex - مرگ و میر ناشی از سیگنالینگ پیچیدهMAPA - نقشهFas-associated protein with death domain - پروتئین مرتبط با Fas با دامنه مرگextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Negative control of TRAIL-R1 signaling by transforming growth factor β1 in pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1 Negative control of TRAIL-R1 signaling by transforming growth factor β1 in pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1](/preview/png/5509412.png)
چکیده انگلیسی
In TGFβ-responsive Panc1 and Colo357 cells, TGFβ1 reduced total and plasma membrane-associated levels of TRAIL-R1 but not those of TRAIL-R2. Consistent with the known predominant role of TRAIL-R1 in TRAIL-mediated signaling in PDAC, TGFβ1 inhibited TRAIL-induced DISC formation and apoptosis as well as phosphorylation of MAPKs and IκBα. Similarly, it also reduced signaling of TRAIL-R1 following its specific activation with an agonistic antibody. In contrast, specific TRAIL-R2 signaling remained unchanged. The TGFβ1 effect on TRAIL-R1 expression was mimicked by ectopic expression of a kinase-active version of the TGFβ type I receptor ALK5 (ALK5-T204D) but not by ALK5 double mutant lacking the ability to phosphorylate Smad proteins (RImL45-T204D). Moreover, TGFβ regulation of TRAIL-R1 was absent in two PDAC cell lines lacking the Smad4 gene DPC4 and siRNA-mediated silencing of Smad4 in Smad4-positive Panc1 cells abolished the TGFβ-mediated decrease in TRAIL-R1 expression, together showing that ALK5/Smad4 signaling is crucial for TGFβ regulation of TRAIL-R1 expression. Our results suggest a novel tumor-promoting function of TGFβ1. By downregulating TRAIL-R1, TGFβ1 may not only promote tumor escape from immune surveillance but also negatively impact on TRAIL- or TRAIL-R1-based therapy regimens for treatment of PDAC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 28, Issue 11, November 2016, Pages 1652-1662
Journal: Cellular Signalling - Volume 28, Issue 11, November 2016, Pages 1652-1662
نویسندگان
David I. Radke, Hendrik Ungefroren, Ole Helm, Susann Voigt, Gökhan Alp, Hendrik Braun, Sebastian Hübner, Janine Dilchert, Susanne Sebens, Dieter Adam, Holger Kalthoff, Anna Trauzold,