Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBP alpha expression

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00473109" target="_blank" >RIV/68378050:_____/16:00473109 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1126/scitranslmed.aad6066" target="_blank" >http://dx.doi.org/10.1126/scitranslmed.aad6066</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scitranslmed.aad6066" target="_blank" >10.1126/scitranslmed.aad6066</a>

Result language

angličtina

Original language name

Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBP alpha expression

Original language description

Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBP alpha (CCAAT/enhancer binding protein a) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBP alpha suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBP alpha expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBP alpha expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBP alpha deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBP alpha-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBP alpha is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBP alpha loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBP alpha and high BMI1.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/LK21307" target="_blank" >LK21307: C/EBPg in normal hematopoiesis and acute myeloid leukemia: identification of the molecular mechanisms involved in cellular transformation</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Science Translational Medicine

ISSN

1946-6234

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

350

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

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UT code for WoS article

000380780000006

EID of the result in the Scopus database

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