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

The result's identifiers

  • 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>

Alternative languages

  • 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

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10700 - Other natural sciences

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

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

Data specific for result type

  • 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