2026-08-29T15:34:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/85722024-11-29T14:54:24Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
García-Carpizo, Verónica
author
Sarmentero, Jacinto
author
Han, Bomie
author
Graña Castro, Osvaldo
author
Ruiz-Llorente, Sergio
author
Pisano, David G
author
Serrano Marugan, Manuel
author
Brooks, Harold B
author
Campbell, Robert M
author
Barrero, Maria Jose
funder
Eli Lilly
2019-11-11T12:45:18Z
2019-11-11T12:45:18Z
2016-09-08
Sci Rep. 2016;6:32952.
10.1038/srep32952
2045-2322
2045-2322
Scientific reports
27604143
http://hdl.handle.net/20.500.12105/8572
The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. NSD2 knock down combined with MEK or BRD4 inhibitors causes co-operative inhibitory responses on cell growth. However, while MEK and BRD4 inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition affects the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2 and that contribute to the RAS transcription program. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition are likely to be needed to ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs in lung cancers with NSD2 overexpression.
eng
NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation
journal article
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
URL
https://repisalud.isciii.es/bitstreams/5b714b3c-be1a-46d7-af72-ca146a1446e7/download
File
MD5
085c98016b074252baf20c853d607c6c
2344121
application/pdf
NSD2contributestooncogenic_2016.pdf
URL
https://repisalud.isciii.es/bitstreams/19330df5-34f5-450e-abc7-16c7b2c1cd8c/download
File
MD5
08e17b3d7001cf8492be2ad7e08361e8
1168265
application/pdf
NSD2contributestooncogenic_SUPL_2016.pdf
URL
https://repisalud.isciii.es/bitstreams/83d9c0c7-c4df-41dc-b55f-a242bbcf6f4f/download
File
MD5
384f2de585a7841e452781ae1dbdc689
1082368
application/vnd.ms-excel
NSD2contributestooncogenic_TABLE1_2016.xls
URL
https://repisalud.isciii.es/bitstreams/bffd30f9-ed50-4319-864a-5081df922138/download
File
MD5
882e5a13245a56d31ac3956c73ec9abb
71680
application/vnd.ms-excel
NSD2contributestooncogenic_TABLE2_2016.xls
URL
https://repisalud.isciii.es/bitstreams/b406c9c7-72e1-4f62-a813-6992bf6645ce/download
File
MD5
43d360cd045e83faf6bf835bf178557a
107520
application/vnd.ms-excel
NSD2contributestooncogenic_TABLE4_2016.xls
URL
https://repisalud.isciii.es/bitstreams/20c7305f-1a96-42bb-a65b-aef1a69a847e/download
File
MD5
92575096cec78896417dc5c96714d7ec
40960
application/vnd.ms-excel
NSD2contributestooncogenic_TABLE5_2016.xls
URL
https://repisalud.isciii.es/bitstreams/16c4dfed-1dbf-4911-938d-15b6b75b6ba3/download
File
MD5
3d0c87e30062d1af0d6557d7ca602945
76591
text/plain
NSD2contributestooncogenic_2016.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/c11e9c52-8db7-4427-8f15-16f1b5220eee/download
File
MD5
08ff1b2b2f1a666642982a23903af48e
19337
text/plain
NSD2contributestooncogenic_SUPL_2016.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/cad6c83e-1b83-4114-afc0-3a79d15dc2fc/download
File
MD5
064f5ff3e9aa2c6de7ce8c9e254c0b7d
100000
text/plain
NSD2contributestooncogenic_TABLE1_2016.xls.txt
URL
https://repisalud.isciii.es/bitstreams/aaafbbb0-29d4-4760-98de-9cd37c4680cc/download
File
MD5
e47983de09473ac76e7fde26d35fb10f
10460
text/plain
NSD2contributestooncogenic_TABLE2_2016.xls.txt
URL
https://repisalud.isciii.es/bitstreams/e93bd1cf-005d-4cee-abf1-00d2ec70108d/download
File
MD5
7c4e26c491db0d778c7f8f83da440dac
30677
text/plain
NSD2contributestooncogenic_TABLE4_2016.xls.txt
URL
https://repisalud.isciii.es/bitstreams/0d2bc760-8e22-476a-be54-6ec3e3c335c8/download
File
MD5
26e09c71817667f5aee4230f13a07bf3
2263
text/plain
NSD2contributestooncogenic_TABLE5_2016.xls.txt