کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10903846 | 1086531 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis
ترجمه فارسی عنوان
شواهد تجربی از میگفیلین به عنوان یک هدف جدید درمانی متاستاز کارسینوم هپاتوسلولار
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کلمات کلیدی
PKGcAMP-dependent kinasefascin-1ROCK-1VASPPBGDpKaNSCECMERK1/2 - ERK1 / 2Invasion - تهاجمExtracellular matrix - ماتریکس خارج سلولیMetastasis - متاستاز Vasodilator stimulated phosphoprotein - واسوادولاتور فسفو پروتئین را تحریک می کندcGMP-dependent protein kinase - پروتئین کیناز وابسته به cGMPporphobilinogen deaminase - پورفبیلینوژن دامینازAdhesion - چسبندگیHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
چکیده انگلیسی
Migfilin is a novel cell-matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell-matrix and cell-cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin׳s role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin׳s expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal-regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis in vitro, providing the molecular mechanism involved and presenting Migfilin as potential therapeutic target against HCC metastasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 334, Issue 2, 10 June 2015, Pages 219-227
Journal: Experimental Cell Research - Volume 334, Issue 2, 10 June 2015, Pages 219-227
نویسندگان
Vasiliki Gkretsi, Dimitrios P. Bogdanos,