The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner.

Meinhardt, Anna-Lena; Munkhbaatar, Enkhtsetseg; Höckendorf, Ulrike; Dietzen, Michelle; Dechant, Marta; Anton, Martina; Jacob, Anne; Steiger, Katja; Weichert, Wilko; Brcic, Luka; McGranahan, Nicholas; Branca, Caterina; Kaufmann, Thomas; Dengler, Michael A; Jost, Philipp J (2022). The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner. Oncogene, 41(9), pp. 1376-1382. Springer Nature 10.1038/s41388-021-02161-1

[img]
Preview
Text
Kaufmann_The_BCL-_family_member_BOK_promotes_KRAS-driven_lung_cancer.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

A variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored the function of BOK in a mutant KrasG12D-driven murine model of lung cancer. Using KrasG12D/+ Bok-/- mice, we observed an overall tumor-promoting function of BOK in vivo. Specifically, loss of BOK reduced proliferation both in cell lines in vitro as well as in KrasG12D-driven tumor lesions in vivo. During tumor development in vivo, loss of BOK resulted in a lower tumor burden, with fewer, smaller, and less advanced tumors. Using KrasG12D/+ Tp53Δ/Δ Bok-/- mice, we identified that this phenotype was entirely dependent on the presence of functional p53. Furthermore, analysis of a human dataset of untreated early-stage lung tumors did not identify any common deletion of the BOK locus, independently of the TP53 status or the histopathological classification. Taken together our data indicate that BOK supports tumor progression in Kras-driven lung cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Kaufmann, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-5594

Publisher:

Springer Nature

Language:

English

Submitter:

Celine Joray

Date Deposited:

24 Feb 2022 13:48

Last Modified:

28 Feb 2022 00:14

Publisher DOI:

10.1038/s41388-021-02161-1

PubMed ID:

35091677

BORIS DOI:

10.48350/165444

URI:

https://boris.unibe.ch/id/eprint/165444

Actions (login required)

Edit item Edit item
Provide Feedback