کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5552019 1557875 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Restore the brake on tumor progression
ترجمه فارسی عنوان
بازسازی ترمز در پیشرفت تومور
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
چکیده انگلیسی

Sonic hedgehog (Shh) signaling plays a key role in regulation of normal development. The negative feedback mechanism mediated by the transcriptional factor, Gli3, acts to finely tune Shh signaling, providing tight control of normal developmental processes. Hyperactivation of Shh signaling often leads to many human malignancies, including basal cell carcinoma and medulloblastoma (MB). However, how tumor cells sustain the aberrant activation of Shh signaling is still not completely understood. We recently revealed that during MB formation, tumor cells express Nestin, a type VI intermediate filament protein, which maintains uncontrolled Shh signaling by abolishing negative feedback by Gli3. Therefore, Nestin expression is a necessary step for MB formation. These findings highlight the novel function of Nestin in regulating Shh signaling, as well as the important role of a disrupted negative feedback mechanism in MB tumorigenesis. Further, restoration of the intrinsic negative feedback by repressing Nestin expression represents a promising approach to treat MB as well as other Shh signaling associated malignancies.

A model for medulloblastoma tumorigenesis. Nestin expression is indispensable for Shh type medulloblastoma tumorigenesis. To achieve this, Nestin augments Shh signaling in medulloblastoma cells by abolishing Gli3-mediated negative feedback mechanism.137

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 138, 15 August 2017, Pages 1-6
نویسندگان
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