Browsing by Author "Ensarioglu H.K."

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    Loss of Wasl improves pancreatic cancer outcome
    (American Society for Clinical Investigation, 2020) Hidalgo-Sastre A.; Desztics J.; Dantes Z.; Schulte K.; Ensarioglu H.K.; Bassey-Archibong B.; Öllinger R.; Engleiter T.; Rayner L.; Einwächter H.; Daniel J.M.; Altaee A.S.A.; Steiger K.; Lesina M.; Rad R.; Reichert M.; Von Figura G.; Siveke J.T.; Schmid R.M.; Lubeseder-Martellato C.
    Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3β, as well as YAP1 and phosphorylated β-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/β-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients. © 2020, American Society for Clinical Investigation.
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    Sensitive and reliable lab-on-paper biosensor for label-free detection of exosomes by electrochemical impedance spectroscopy
    (Springer, 2024) Sazaklioglu S.A.; Torul H.; Tamer U.; Ensarioglu H.K.; Vatansever H.S.; Gumus B.H.; Çelikkan H.
    A new, sensitive, and cost-effective lab-on-paper-based immunosensor was designed based on electrochemical impedance spectroscopy (EIS) for the detection of exosomes. EIS was selected as the determination method since there was a surface blockage in electron transfer by binding the exosomes to the transducer. Briefly, the carbon working electrode (WE) on the paper electrode (PE) was modified with gold particles (AuPs@PE) and then conjugated with anti-CD9 (Anti-CD9/AuPs@PE) for the detection of exosomes. Variables involved in the biosensor design were optimized with the univariate mode. The developed method presents the limit of detection of 8.7 × 102 exosomes mL−1, which is lower than that of many other available methods under the best conditions. The biosensor was also tested with urine samples from cancer patients with high recoveries. Due to this a unique, low-cost, biodegradable technology is presented that can directly measure exosomes without labeling them for early cancer or metastasis detection. Graphical abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2024.