TY  - JOUR
AU  - Ramesh, Palaniappan
AU  - Al Kadi, Amal R
AU  - Borse, Gaurav M
AU  - Webendörfer, Maximilian
AU  - Zaun, Gregor
AU  - Metzenmacher, Martin
AU  - Doerr, Fabian
AU  - Bölükbas, Servet
AU  - Hegedüs, Balazs
AU  - Lueong, Smiths S
AU  - Magne, Joelle
AU  - Liu, Beiyun
AU  - Nunez, Greisly
AU  - Schuler, Martin
AU  - Green, Douglas R
AU  - Kalkavan, Halime
TI  - BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK.
JO  - Cells
VL  - 14
IS  - 4
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2025-00446
SP  - 246
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Lung Neoplasms: pathology
KW  - Lung Neoplasms: metabolism
KW  - Lung Neoplasms: genetics
KW  - Neoplasm Invasiveness
KW  - Proto-Oncogene Proteins c-bcl-2: metabolism
KW  - Apoptosis
KW  - Cell Line, Tumor
KW  - Epithelial-Mesenchymal Transition: genetics
KW  - Mitochondrial Membranes: metabolism
KW  - BCL-2 family (Other)
KW  - BCL-B (Other)
KW  - BOK (Other)
KW  - DTP (Other)
KW  - EMT (Other)
KW  - cancer (Other)
KW  - drug-resistance (Other)
KW  - invasiveness (Other)
KW  - mitochondrial permeabilization (Other)
KW  - persister phenotype (Other)
KW  - Proto-Oncogene Proteins c-bcl-2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39996719
C2  - pmc:PMC11853756
DO  - DOI:10.3390/cells14040246
UR  - https://inrepo02.dkfz.de/record/299486
ER  -