کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10747923 1050254 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells
چکیده انگلیسی
Cancer metastasis is strongly correlated with epithelial-mesenchymal transition (EMT), in which transforming growth factor-β (TGF-β) signaling plays a central role. CD44 has emerged as a cancer stem cell (CSC) marker that strongly induces EMT together with TGF-β1. This study aimed to investigate the link between high CD44 and TGF-β1 levels during EMT in HCC cell lines. FACS analysis showed high expression of CD44 in TGF-β1-positive SNU-368 cells and TGF-β1-negative SNU-354 cells. SNU-368 CD44+ cells showed EMT through up-regulation of the AKT/GSK-3β/β-catenin pathway. By comparison, SNU-354 CD44+ cells showed only increased N-cadherin expression, which was not accompanied by a decrease in E-cadherin expression, and also down-regulated the AKT/GSK-3β/β-catenin pathway. However, TGF-β1-stimulated SNU-354 cells (CD44/TGF-β1+) exhibited lower E-cadherin and higher N-cadherin expression with increased AKT/GSK-3β/β-catenin pathway activity. CD44/TGF-β1+ SNU-354 cells also showed enhanced migration and formed larger spheres, while the TGF-β1-induced stem cell properties returned to their original state with the TGF-β1 inhibitor SB431542. SB431542-treated SNU-368 (CD44/TGF-β1-) cells also showed diminished N-cadherin and AKT/GSK-3β/β-catenin pathway activity and further decreased cell motility in a wound healing assay. However, CD44 knockdown in SNU-354 cells did not induce EMT even after treatment with TGF-β1. Finally, double inhibition of both CD44 and TGF-β1 further decreased migration and sphere formation more strongly than a single inhibition in SNU-368 cells. In conclusion, the current study demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 477, Issue 4, 2 September 2016, Pages 568-574
نویسندگان
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