BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity 

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F16%3AN0000141" target="_blank" >RIV/00098892:_____/16:N0000141 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/16:33160118 RIV/00023884:_____/16:#0006926

Result on the web

<a href="https://www.nature.com/articles/ncomms13398.pdf" target="_blank" >https://www.nature.com/articles/ncomms13398.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ncomms13398" target="_blank" >10.1038/ncomms13398</a>

Result language

angličtina

Original language name

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity 

Original language description

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10700 - Other natural sciences

Project

—

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

Nature Communications

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

November

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

13398

UT code for WoS article

000387972000001

EID of the result in the Scopus database

2-s2.0-84995428246