Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Belharazem D, Grass A, Paul C, Vitacolonna M, Schalke B, Rieker R, Koerner D, Jungebluth P, Simon-Keller K, Hohenberger P, Roessner EM, Wiebe K, Graeter T, Kyriss T, Ott G, Geserick P, Leverkus M, Stroebel P, Marx A
Zeitschrift: Oncotarget
Jahr der Veröffentlichung: 2017
Band: 8
Heftnummer: 52
Seitenbereich: 89580-89594
ISSN: 1949-2553


Abstract

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1high thymomas and TCs.


FAU-Autoren / FAU-Herausgeber

Rieker, Ralf Prof. Dr.
Pathologisches Institut


Autor(en) der externen Einrichtung(en)
Georg-August-Universität Göttingen
Klinik Löwenstein gGmbH
Robert Bosch GmbH
Robert-Bosch-Krankenhaus
Ruprecht-Karls-Universität Heidelberg
Universität Regensburg
Westfälische Wilhelms-Universität (WWU) Münster


Zitierweisen

APA:
Belharazem, D., Grass, A., Paul, C., Vitacolonna, M., Schalke, B., Rieker, R.,... Marx, A. (2017). Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling. Oncotarget, 8(52), 89580-89594. https://dx.doi.org/10.18632/oncotarget.15929

MLA:
Belharazem, Djeda, et al. "Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling." Oncotarget 8.52 (2017): 89580-89594.

BibTeX: 

Zuletzt aktualisiert 2019-25-04 um 14:57