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Munkhbaatar, E.* ; Dietzen, M.* ; Agarwal, D.* ; Anton, M.* ; Jesinghaus, M.* ; Boxberg, M.* ; Pfarr, N.* ; Bidola, P.* ; Uhrig, S.* ; Höckendorf, U.* ; Meinhardt, A.L.* ; Wahida, A.* ; Heid, I.* ; Braren, R.* ; Mishra, R.* ; Warth, A.* ; Muley, T.* ; Poh, P.S.P.* ; Wang, X.* ; Fröhling, S.* ; Steiger, K.* ; Slotta-Huspenina, J.* ; van Griensven, M.* ; Pfeiffer, F.* ; Lange, S.* ; Rad, R.* ; Spella, M.* ; Stathopoulos, G.T. ; Ruland, J.* ; Bassermann, F.* ; Weichert, W.* ; Strasser, A.* ; Branca, C.* ; Heikenwalder, M.* ; Swanton, C.* ; McGranahan, N.* ; Jost, P.J.*

MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Nat. Commun. 11:4527 (2020)
Publ. Version/Full Text DOI PMC
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Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Bcl-2 Family; Cancer; Survival; Kras; Proteins; Mouse; Lymphocytes; Expression; Inhibitors; Docetaxel
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 4527 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-501600-003
Grants Projekt DEAL
DOI 10.1038/s41467-020-18372-1
WOS ID WOS:000607107700004
Scopus ID 85090501561
PubMed ID 32913197
Erfassungsdatum 2020-10-29
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