کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815257 | 1058462 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nodal signals via β-arrestins and RalGTPases to regulate trophoblast invasion
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کلمات کلیدی
β-arrestins(TGF-β)G protein-coupled receptors - G گیرنده های پروتئینی همراهtransforming growth factor - تبدیل فاکتور رشدTrophoblast - تروفوبلاستInvasion - تهاجمPlacenta - جفت Nodal - طبیعیsmad anchor for receptor activation - لنگر مهار برای فعال شدن گیرندهmitogen-activated protein kinases - کیناز پروتئین فعال Mitogen
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Placentation is critical for establishing a healthy pregnancy. Trophoblasts mediate implantation and placentation and certain subtypes, most notably extravillous cytotrophoblast, are highly invasive. Trophoblast invasion is tightly regulated by microenvironmental cues that dictate placental morphology and depth. In choriocarcinomas, malignant trophoblast cells become hyperinvasive, breaching the myometrium and leading to major complications. Nodal, a member of the TGF-β superfamily, is expressed throughout the endometrium during the peri-implantation period and in invasive trophoblast cells. Nodal promotes the invasion of numerous types of cancer cells. However, Nodal's role in trophoblast and choriocarcinoma cell invasion is unclear. Here we show that Nodal stimulates the invasion of both the non-malignant HTR-8SV/neo trophoblast and JAR choriocarcinoma cells in a dose-dependent manner. We found that endogenous β-arrestins and Ral GTPases, key regulators of the cell cytoskeleton, are constitutively associated with Nodal receptors (ALK4 and ALK7) in trophoblast cells and that RalA is colocalized with ALK4 in endocytic vesicles. Nodal stimulates endogenous β-arrestin2 to associate with phospho-ERK1/2, and knockdown of β-arrestin or Ral proteins impairs Nodal-induced trophoblast and choriocarcinoma cell invasion. These results demonstrate, for the first time, that β-arrestins and RalGTPases are important regulators of Nodal-induced invasion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 1935-1942
Journal: Cellular Signalling - Volume 26, Issue 9, September 2014, Pages 1935-1942
نویسندگان
Jeffrey Law, Guihua Zhang, Magdalena Dragan, Lynne-Marie Postovit, Moshmi Bhattacharya,