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https://hdl.handle.net/2445/179794
Title: | SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade |
Author: | Romero, Octavio A. Vilarrubi, Andrea Alburquerque Bejar, Juan J. Gomez, Antonio Andrades, Alvaro Trastulli, Deborah Pros, Eva Setien, Fernando Verdura, Sara Farré, Lourdes Martín-Tejera, Juan F. Llabata, Paula Oaknin, Ana Saigí, Maria Piulats, Josep M. Matias-Guiu, Xavier Medina, Pedro P. Vidal, August Villanueva Garatachea, Alberto Sánchez Céspedes, Montserrat |
Keywords: | Càncer Antioncogens Epigenètica Tumors Cancer Antioncogenes Epigenetics Tumors |
Issue Date: | 14-Jul-2021 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-021-24618-3 |
It is part of: | Nature Communications, 2021, vol. 12, num. 4319 |
URI: | https://hdl.handle.net/2445/179794 |
Related resource: | https://doi.org/10.1038/s41467-021-24618-3 |
Appears in Collections: | Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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