کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5509380 1538512 2017 29 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells
چکیده انگلیسی
Previous studies have shown that leptin, an adipocyte-secreted hormone, stimulates ovarian cancer invasion. Here, we investigated the contribution of uPA in leptin-induced ovarian cancer cell invasion. The cell invasion and migration experiments were carried out using matrigel invasion and wound healing assays in ovarian cancer cell lines (OVCAR3, SKOV3and CaoV-3). The mechanism underlying the invasive effect of leptin was examined using cell transfection with Ob-Rb siRNA, pre-treatment with a specific inhibitor of RhoA and ROCK, RhoA activation assay, OB-Rb, Rock and upA protein expression. Our results show that leptin induced ovarian cancer cell invasion via up-regulating upA in a time and dose-dependent manner, which was attenuated using knockdown of OB-Rb by siRNA. Moreover, pre-incubation with C3 (inhibitor of RhoA) and Y-27632 (inhibitor of ROCK) effectively attenuated leptin-induced upA expression and inhibited invasive ability of ovarian cancer cells. We also found that pretreatment with inhibitors of PI3K/AKT (LY294002), JAK/STAT (AG490) and NF-kB (BAY 11-7082) significantly reduced leptin-induced upA expression. Collectively, our findings demonstrate that OB-Rb, RhoA/ROCK, PI3K/AKT, JAK/STAT pathways and NF-kB activation are involved in leptin-induced upA expression. These results may provide a new mechanism that facilitates leptin-induced ovarian cancer invasion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 32, April 2017, Pages 104-114
نویسندگان
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