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Status: Bibliographieeintrag

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Verfasst von:Urbanik, Toni [VerfasserIn]   i
 Köhler, Bruno Christian [VerfasserIn]   i
 Boger, Regina [VerfasserIn]   i
 Wörns, Marcus Alexander [VerfasserIn]   i
 Heeger, Steffen [VerfasserIn]   i
 Otto, Gerhard [VerfasserIn]   i
 Hövelmeyer, Nadine [VerfasserIn]   i
 Galle, Peter Robert [VerfasserIn]   i
 Schuchmann, Marcus [VerfasserIn]   i
 Waisman, Ari [VerfasserIn]   i
 Schulze-Bergkamen, Henning [VerfasserIn]   i
Titel:Down-regulation of CYLD as a trigger for NF-κB activation and a mechanism of apoptotic resistance in hepatocellular carcinoma cells
Verf.angabe:Toni Urbanik, Bruno Christian Köhler, Regina Johanna Boger, Marcus Alexander Wörns, Steffen Heeger, Gerd Otto, Nadine Hövelmeyer, Peter Robert Galle, Marcus Schuchmann, Ari Waisman and Henning Schulze-Bergkamen
E-Jahr:2011
Jahr:January 1, 2011
Umfang:11 S.
Fussnoten:Gesehen am 01.12.2022
Titel Quelle:Enthalten in: International journal of oncology
Ort Quelle:Athens : Spandidos Publ., 2001
Jahr Quelle:2011
Band/Heft Quelle:38(2011), 1 vom: Jan., Seite 121-131
ISSN Quelle:1791-2423
Abstract:The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins. In order to investigate the role of CYLD in apoptotic signaling in human hepatocellular carcinoma (HCC) cells, we first studied the expression levels of CYLD in HCC tissues. CYLD expression was lower in HCC both at protein and mRNA levels compared to the surrounding non-malignant tissue. In order to further study the role of CYLD in the apoptotic sensitivity of HCC cells, CYLD was specifically down-regulated in HCC cell lines via RNA interference. The specific down-regulation of CYLD resulted in increased resistance towards treatment with doxorubicin, 5-fluorouracil and cisplatin. In addition, the down-regulation of CYLD in HCC cells decreased the sensitivity towards tumor necrosis factor-α-induced apoptosis. The CYLD knockdown also led to the degradation of the NF-κB inhibitor, IκB-α, resulting in enhanced NF-κB activity in HCC cells. Finally, we found that CYLD expression was triggered by the multikinase inhibitor, sorafenib, by the inhibition of Raf-1, as well as by the blockage of the pro-survival kinases, MEK (U0126) and the epidermal growth factor receptor (AG1478). In summary, we show that CYLD is down-regulated in human HCC and is involved in the apoptotic resistance of HCC cells. Our data indentify the reconstitution of CYLD expression as an attractive approach for overcoming resistance to treatment in HCC.
DOI:doi:10.3892/ijo_00000831
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.3892/ijo_00000831
 Volltext: https://www.spandidos-publications.com/10.3892/ijo_00000831
 DOI: https://doi.org/10.3892/ijo_00000831
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1824122640
Verknüpfungen:→ Zeitschrift

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