کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10915417 | 1089950 | 2016 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway-Driven Intestinal Neoplasia
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کلمات کلیدی
ERMezrin-radixin-moesinNa+/H+H&E - H & EYAP - ایجادImmunofluorescence - ایمونوفلورسانسImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیSmall intestine - روده کوچکColorectal cancer - سرطان روده بزرگintestinal epithelial cell - سلول های اپیتلیال رودهPlasma membrane - غشای پلاسماHematoxylin and Eosin - هماتوکسیلین و ائوزینCRC - کد افزونگی دورهای IEC - کمیسیون مستقل انتخابات
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
NHERF1/EBP50, an adaptor molecule that interacts with β-catenin, YAP, and PTEN, has been recently implicated in the progression of various human malignancies, including colorectal cancer. We report here that NHERF1 acts as a tumor suppressor in vivo for intestinal adenoma development. NHERF1 is highly expressed at the apical membrane of mucosa intestinal epithelial cells (IECs) and serosa mesothelial cells. NHERF1-deficient mice show overall longer small intestine and colon that most likely could be attributed to a combination of defects, including altered apical brush border of absorbtive IECs and increased number of secretory IECs. NHERF1 deficiency in ApcMin/+ mice resulted in significantly shorter animal survival due to markedly increased tumor burden. This resulted from a moderate increase of the overall tumor density, more pronounced in females than males, and a massive increase in the number of large adenomas in both genders. The analysis of possible pathways controlling tumor size showed upregulation of Wnt-β-catenin pathway, higher expression of unphosphorylated YAP, and prominent nuclear expression of cyclin D1 in NHERF1-deficient tumors. Similar YAP changes, with relative decrease of phosphorylated YAP and increase of nuclear YAP expression, were observed as early as the adenoma stages in the progression of human colorectal cancer. This study discusses a complex role of NHERF1 for intestinal morphology and presents indisputable evidence for its in vivo tumor suppressor function upstream of Wnt-β-catenin and Hippo-YAP pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 18, Issue 8, August 2016, Pages 512-523
Journal: Neoplasia - Volume 18, Issue 8, August 2016, Pages 512-523
نویسندگان
Maria-Magdalena Georgescu, Mihai Gagea, Gilbert Cote,