PuSH - Publikationsserver des Helmholtz Zentrums München: IkB kinase a Is required for development and progression of KRAS-mutant lung adenocarcinoma.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Vreka, M. ; Lilis, I.* ; Papageorgopoulou, M. ; Giotopoulou, G.A. ; Lianou, M.* ; Giopanou, I.* ; Kanellakis, N.I.* ; Spella, M.* ; Agalioti, T.* ; Armenis, V.* ; Goldmann, T.* ; Marwitz, S.* ; Yull, F.E.* ; Blackwell, T.S.* ; Pasparakis, M.* ; Marazioti, A.* ; Stathopoulos, G.T.

IkB kinase a Is required for development and progression of KRAS-mutant lung adenocarcinoma.

Cancer Res. 78, 2939-2951 (2018)

Verlagsversion

Postprint

DOI

PMC

	Open Access Green

Abstract
Metriken
Zusatzinfos

Although oncogenic activation of NFkB has been identified in various tumors, the NFkB–activating kinases (inhibitor of NFkB kinases, IKK) responsible for this are elusive. In this study, we determined the role of IKKa and IKKb in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane and by respiratory epithelial expression of oncogenic KRASG12D. Using NFkB reporter mice and conditional deletions of IKKa and IKKb, we identified two distinct early and late activation phases of NFkB during chemical and genetic lung adenocarcinoma development, which were characterized by nuclear translocation of RelB, IkBb, and IKKa in tumor-initiated cells. IKKa was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung adenocarcinoma, and respiratory epithelial IKKa-deficient mice were markedly protected from the disease. IKKa specifically cooperated with mutant KRAS for tumor induction in a cell-autonomous fashion, providing mutant cells with a survival advantage in vitro and in vivo. IKKa was highly expressed in human lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK function delivered superior effects against KRAS-mutant lung adenocarcinoma compared with a specific IKKb inhibitor. These results demonstrate an actionable requirement for IKKa in KRAS-mutant lung adenocarcinoma, marking the kinase as a therapeutic target against this disease. Significance: These findings report a novel requirement for IKKa in mutant KRAS lung tumor formation, with potential therapeutic applications.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

9.130

1.692