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Reptin drives tumour progression and resistance to chemotherapy in nonsmall cell lung cancer

While targeted nonsmall cell lung cancer (NSCLC) therapies have improved the outcome of defined disease subtypes, prognosis for most patients remains poor. We found the AAA+ ATPase Reptin to be highly expressed in the vast majority of 278 NSCLC tumour samples. Thus, the objective of the study was to...

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Main Authors: Mikesch, Jan-Henrik (Author) , Schwammbach, Daniela (Author) , Hartmann, Wolfgang (Author) , Schmidt, Lars H. (Author) , Schliemann, Christoph (Author) , Angenendt, Linus (Author) , Wiewrodt, Rainer (Author) , Marra, Alessandro (Author) , Thoennissen, Nils H. (Author) , Wardelmann, Eva (Author) , Köhler, Gabriele (Author) , Lenz, Georg (Author) , Müller-Tidow, Carsten (Author) , Berdel, Wolfgang E. (Author) , Arteaga, Maria-Francisca (Author)
Format: Article (Journal)
Language:English
Published: 11 July 2018
In: The European respiratory journal
Year: 2018, Volume: 52, Issue: 1, Pages: 1-11
ISSN:1399-3003
DOI:10.1183/13993003.01637-2017
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1183/13993003.01637-2017
Verlag, kostenfrei, Volltext: https://publications.ersnet.org/content/erj/52/1/1701637
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Author Notes:Jan-Henrik Mikesch, Daniela Schwammbach, Wolfgang Hartmann, Lars H. Schmidt, Christoph Schliemann, Linus Angenendt, Rainer Wiewrodt, Alessandro Marra, Nils H. Thoennissen, Eva Wardelmann, Gabriele Köhler, Georg Lenz, Carsten Müller-Tidow, Wolfgang E. Berdel and Maria-Francisca Arteaga
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Summary:While targeted nonsmall cell lung cancer (NSCLC) therapies have improved the outcome of defined disease subtypes, prognosis for most patients remains poor. We found the AAA+ ATPase Reptin to be highly expressed in the vast majority of 278 NSCLC tumour samples. Thus, the objective of the study was to assess the role of Reptin in NSCLC.Survival analyses of 1145 NSCLC patients revealed that high RNA expression levels of Reptin are associated with adverse outcome. Knockdown of Reptin in human NSCLC cells impaired growth ex vivo and eliminated engraftment in a xenograft model. Reptin directly interacted with histone deacetylase 1 (HDAC1) as the critical mechanism driving NSCLC tumour progression. Pharmacological disruption of the Reptin/HDAC1 complex resulted in a substantial decrease in NSCLC cell proliferation and induced significant sensitisation to cisplatin.Our results identify Reptin as a novel independent prognostic factor and as a key regulator mediating proliferation and clonal growth of human NSCLC cells ex vivo and in vivo We unveil a Reptin/HDAC1 protein complex whose pharmacological disruption sensitises NSCLC cells to cisplatin, suggesting this approach for application in clinical trials.
Item Description:Gesehen am 16.04.2020
Physical Description:Online Resource
ISSN:1399-3003
DOI:10.1183/13993003.01637-2017

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