PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Spella, M. ; Ntaliarda, G. ; Skiadas, G. ; Lamort, A.-S. ; Vreka, M. ; Marazioti, A. ; Lilis, I. ; Bouloukou, E. ; Giotopoulou, G.A. ; Pepe, M. ; Weiss, S.A. ; Petrera, A. ; Hauck, S.M. ; Koch, I.* ; Lindner, M.* ; Hatz, R.A.* ; Behr, J.* ; Arendt, K.A.M. ; Giopanou, I. ; Brunn, D.* ; Savai, R.* ; Jenne, D. ; de Château, M.* ; Yull, F.E.* ; Blackwell, T.S.* ; Stathopoulos, G.T.

Non-oncogene addiction of KRAS-mutant cancers to IL-1β via versican and mononuclear IKKβ.

Cancers 15:23 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Kirsten rat sarcoma virus (KRAS)-mutant cancers are frequent, metastatic, lethal, and largely undruggable. While interleukin (IL)-1β and nuclear factor (NF)-κB inhibition hold promise against cancer, untargeted treatments are not effective. Here, we show that human KRAS-mutant cancers are addicted to IL-1β via inflammatory versican signaling to macrophage inhibitor of NF-κB kinase (IKK) β. Human pan-cancer and experimental NF-κB reporter, transcriptome, and proteome screens reveal that KRAS-mutant tumors trigger macrophage IKKβ activation and IL-1β release via secretory versican. Tumor-specific versican silencing and macrophage-restricted IKKβ deletion prevents myeloid NF-κB activation and metastasis. Versican and IKKβ are mutually addicted and/or overexpressed in human cancers and possess diagnostic and prognostic power. Non-oncogene KRAS/IL-1β addiction is abolished by IL-1β and TLR1/2 inhibition, indicating cardinal and actionable roles for versican and IKKβ in metastasis.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.200
0.000
1
1
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Bioluminescence ; Cancer ; Inflammation ; Interleukin-1β ; Non-oncogene Addiction ; Nuclear Factor-κb; Kappa-b Activation; Mouse Model; Mast-cells; T-cells; Lung; Immune; Mice; Inflammation; Antagonist; Inhibitors
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2072-6694
Zeitschrift Cancers
Quellenangaben Band: 15, Heft: 6, Seiten: , Artikelnummer: 23 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Lung Research

Enabling and Novel Technologies
PSP-Element(e) G-501600-003
G-501600-001
G-501600-005
A-630700-001
G-505700-001
Förderungen Deutsches Zentrum fur Lungenforschung
Bundesministerium fur Bildung und Forschung grant ALTERNATIVE
Deutsche Forschungsgemeinschaft Graduiertenkolleg
European Research Council 2015 Proof of Concept grant
European Research Council 2010 Starting Independent Investigator grant
Department of Veteran Affairs
National Institutes of Health
Buzzard Pharmaceuticals
Hellenic Foundation for Research and Innovation
General Secretariat for Research and Innovation
DOI 10.3390/cancers15061866
WOS ID 000968443900001
Scopus ID 85151413428
PubMed ID 36980752
Erfassungsdatum 2023-10-06
[➜Korrektur melden]