%0 Journal Article
%A Ramesh, Palaniappan
%A Al Kadi, Amal R
%A Borse, Gaurav M
%A Webendörfer, Maximilian
%A Zaun, Gregor
%A Metzenmacher, Martin
%A Doerr, Fabian
%A Bölükbas, Servet
%A Hegedüs, Balazs
%A Lueong, Smiths S
%A Magne, Joelle
%A Liu, Beiyun
%A Nunez, Greisly
%A Schuler, Martin
%A Green, Douglas R
%A Kalkavan, Halime
%T BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK.
%J Cells
%V 14
%N 4
%@ 2073-4409
%C Basel
%I MDPI
%M DKFZ-2025-00446
%P 246
%D 2025
%X Expression of BCL-B, an anti-apoptotic BCL-2 family member, is correlated with worse survival in lung adenocarcinomas. Here, we show that BCL-B can mitigate cell death initiation through interaction with the effector protein BOK. We found that this interaction can promote sublethal mitochondrial outer membrane permeabilization (MOMP) and consequently generate apoptosis-flatliners, which represent a source of drug-tolerant persister cells (DTPs). The engagement of endothelial-mesenchymal-transition (EMT) further promotes cancer cell invasiveness in such DTPs. Our results reveal that BCL-B fosters cancer cell aggressiveness by counteracting complete MOMP.
%K Humans
%K Lung Neoplasms: pathology
%K Lung Neoplasms: metabolism
%K Lung Neoplasms: genetics
%K Neoplasm Invasiveness
%K Proto-Oncogene Proteins c-bcl-2: metabolism
%K Apoptosis
%K Cell Line, Tumor
%K Epithelial-Mesenchymal Transition: genetics
%K Mitochondrial Membranes: metabolism
%K BCL-2 family (Other)
%K BCL-B (Other)
%K BOK (Other)
%K DTP (Other)
%K EMT (Other)
%K cancer (Other)
%K drug-resistance (Other)
%K invasiveness (Other)
%K mitochondrial permeabilization (Other)
%K persister phenotype (Other)
%K Proto-Oncogene Proteins c-bcl-2 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39996719
%2 pmc:PMC11853756
%R 10.3390/cells14040246
%U https://inrepo02.dkfz.de/record/299486