Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 (PAR2) activation, followed by PI3K-AKT activation and GSK3-β inactivation is involved in these processes and that β-catenin a well known tumor regulatory protein, contribute to this signaling pathway. The pivotal role of β-catenin was further indicated by the upregulation of its downstream targets Cyclin D1, c-Myc, COX-2, MMP-7, MMP-14 and Claudin-1. β-catenin knock-down almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer.
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
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Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
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Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
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