BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK

Ramesh, Palaniappan; Al Kadi, Amal, R.; Borse, Gaurav, M.; Webendörfer, Maximilian; Zaun, Gregor; Metzenmacher, Martin; Doerr, Fabian; Bölükbas, Servet; Hegedüs, Balazs; Lueong, Smiths, S.; Magne, Joelle; Liu, Beiyun; Nunez, Greisly; Schuler, Martin; Green, Douglas, R.; Kalkavan, Halime

doi:10.3390/cells14040246

Article / ChapterCC BY 4.0Sun Feb 9 2025

BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK

Ramesh, Palaniappan ; Al Kadi, Amal R.; Borse, Gaurav M.; Webendörfer, Maximilian ; Zaun, Gregor ; Metzenmacher, Martin ; Doerr, Fabian ; Bölükbas, Servet ; Hegedüs, Balazs; Lueong, Smiths S.; Magne, Joelle; Liu, Beiyun; Nunez, Greisly; Schuler, Martin ; Green, Douglas R.; Kalkavan, Halime

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.

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Date Issued:

09.02.2025

URN:

urn:nbn:de:hbz:465-20251023-162033-1

DOI:

10.3390/cells14040246

Language:

English

Type of Resource:

Text

Keywords:

mitochondrial permeabilization

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BCL-2 family

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BCL-B

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BOK

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DTP

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persister phenotype

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EMT

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invasiveness

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drug-resistance

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cancer

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Subject categories of the Deutsche Nationalbibliografie:

610 Medical sciences Medicine

Hosting institution:

Faculty of Medicine, Essen University Hospital, Clinic for Internal Medicine (Tumor Research)

Hosting institution:

Faculty of Medicine, Essen University Hospital, Ruhrlandklinik Essen – Universitätsklinik

funding:

The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.

This work was supported by grants from the German Research Foundation (DFG, KA 4830/1-1), the Advanced Clinician Scientist Programm UMEA² (Medical Faculty, University Duisburg-Essen), the Federal Ministry of Education and Research 01EO2104 (BMBF), the German Cancer Aid (Max-Eder Junior Research Group Program, DKH 70115382) to H.K., by ALSAC (SJCRH), and by the U.S. National Cancer Institute grant R35 CA231620 to D.R.G.

Info on primary publication:

Ramesh, P., Al Kadi, A. R., Borse, G. M., Webendörfer, M., Zaun, G., Metzenmacher, M., Doerr, F., Bölükbas, S., Hegedüs, B., Lueong, S. S., Magne, J., Liu, B., Nunez, G., Schuler, M., Green, D. R., & Kalkavan, H. (2025). BCL-B Promotes Lung Cancer Invasiveness by Direct Inhibition of BOK. Cells, 14(4), 246. https://doi.org/10.3390/cells14040246

Published: 9 February 2025

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