onr:"swepub:oai:prod.swepub.kib.ki.se:134598358"
Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:134598358" > BRCA1-regulated RRM...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02696naa a2200445 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:134598358 | |
| 003 | SwePub | |
| 008 | 240916s2016 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1345983582 URI |
| 024 | 7 | a https://doi.org/10.1038/ncomms133982 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Rasmussen, RD4 aut |
| 245 | 1 0 | a BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity |
| 264 | c 2016-11-15 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2016 |
| 520 | a 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. | |
| 700 | 1 | a Gajjar, MK4 aut |
| 700 | 1 | a Tuckova, L4 aut |
| 700 | 1 | a Jensen, KE4 aut |
| 700 | 1 | a Maya-Mendoza, A4 aut |
| 700 | 1 | a Holst, CB4 aut |
| 700 | 1 | a Mollgaard, K4 aut |
| 700 | 1 | a Rasmussen, JS4 aut |
| 700 | 1 | a Brennum, J4 aut |
| 700 | 1 | a Bartek, Ju Karolinska Institutet4 aut |
| 700 | 1 | a Syrucek, M4 aut |
| 700 | 1 | a Sedlakova, E4 aut |
| 700 | 1 | a Andersen, KK4 aut |
| 700 | 1 | a Frederiksen, MH4 aut |
| 700 | 1 | a Bartek, Ju Karolinska Institutet4 aut |
| 700 | 1 | a Hamerlik, P4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Nature communicationsd : Springer Science and Business Media LLCg 7, s. 13398-q 7<13398-x 2041-1723 |
| 856 | 4 | u https://www.nature.com/articles/ncomms13398.pdf |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:134598358 |
| 856 | 4 8 | u https://doi.org/10.1038/ncomms13398 |
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