PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Meßner, M.* ; Schmitt, S.* ; Ardelt, M.A.* ; Fröhlich, T.* ; Müller, M.* ; Pein, H.* ; Huber-Cantonati, P.* ; Ortler, C.* ; Koenig, L.M.* ; Zobel, L.* ; Koeberle, A.* ; Arnold, G.J.* ; Rothenfußer, S.* ; Kiemer, A.K.* ; Gerbes, A.L.* ; Zischka, H. ; Vollmar, A.M.* ; Pachmayr, J.*

Metabolic implication of tigecycline as an efficacious second-line treatment for sorafenib-resistant hepatocellular carcinoma.

FASEB J. 34, 11860-11882 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Sorafenib represents the current standard of care for patients with advanced-stage hepatocellular carcinoma (HCC). However, acquired drug resistance occurs frequently during therapy and is accompanied by rapid tumor regrowth after sorafenib therapy termination. To identify the mechanism of this therapy-limiting growth resumption, we established robust sorafenib resistance HCC cell models that exhibited mitochondrial dysfunction and chemotherapeutic crossresistance. We found a rapid relapse of tumor cell proliferation after sorafenib withdrawal, which was caused by renewal of mitochondrial structures alongside a metabolic switch toward high electron transport system (ETS) activity. The translation-inhibiting antibiotic tigecycline impaired the biogenesis of mitochondrial DNA-encoded ETS subunits and limited the electron acceptor turnover required for glutamine oxidation. Thereby, tigecycline prevented the tumor relapse in vitro and in murine xenografts in vivo. These results offer a promising second-line therapeutic approach for advanced-stage HCC patients with progressive disease undergoing sorafenib therapy or treatment interruption due to severe adverse events.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.966
1.102
1
7
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Antibiotics ; Electron Acceptor Auxotrophy ; Mitochondrial Biogenesis ; Sorafenib Resistance ; Tumor Relapse; Cancer-cells; Oxidative-phosphorylation; Mitochondrial Biogenesis; Antitumor-activity; Therapy; Proliferation; Translation; Inhibition; Mitophagy; Receptor
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Journal FASEB Journal
Quellenangaben Volume: 34, Issue: 9, Pages: 11860-11882 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Toxicology and Pharmacology (TOX)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505200-003
DOI 10.1096/fj.202001128R
WOS ID WOS:000548010700001
Scopus ID 85089749642
PubMed ID 32652772
Erfassungsdatum 2020-07-28
[➜Report correction]