dc.contributor
Institut Català de la Salut
dc.contributor
[Cebrià-Costa JP, Pascual-Reguant L, Serra-Bardenys G, Querol J, Cosín M, Nuciforo P, Rodilla V, Peiró S] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Gonzalez-Perez A] Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain. [Verde G] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain. [Bernado-Morales C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red en Oncología (CIBERONC), 08035 Barcelona, Spain. [Arribas J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red en Oncología (CIBERONC), 08035 Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Cebrià Costa, Joan Pau
dc.contributor.author
Serra Bardenys, Gemma
dc.contributor.author
Querol, J
dc.contributor.author
Cosín, M
dc.contributor.author
Verde, Gaetano
dc.contributor.author
Nuciforo, Paolo Giovanni
dc.contributor.author
Rodilla Benito, Verónica
dc.contributor.author
Arribas López, Joaquin Vicente
dc.contributor.author
Peiro Sales, Sandra
dc.contributor.author
Bernadó Morales, Cristina
dc.contributor.author
Pascual Reguant, Laura
dc.contributor.author
Gonzalez-Perez, Abel
dc.date.accessioned
2025-10-24T08:13:55Z
dc.date.available
2025-10-24T08:13:55Z
dc.date.issued
2021-11-05T12:47:16Z
dc.date.issued
2021-11-05T12:47:16Z
dc.date.issued
2020-01-02
dc.identifier
Cebrià-Costa JP, Pascual-Reguant L, Gonzalez-Perez A, Serra-Bardenys G, Querol J, Cosín M, et al. LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells. Oncogene. 2020 Jan 2;39(1):79–121.
dc.identifier
https://hdl.handle.net/11351/6508
dc.identifier
10.1038/s41388-019-0969-1
dc.identifier
000509849200007
dc.identifier.uri
https://hdl.handle.net/11351/6508
dc.description.abstract
Cromosomes; Marcadors pronòstics
dc.description.abstract
Cromosomas; Marcadores de pronóstico
dc.description.abstract
Chromosomes; Prognostic markers
dc.description.abstract
Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.
dc.description.abstract
This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI12/01250; CP08/00223; PI16/00253; and CB16/12/00449), MINECO (SAF2013-48849-C2-1-R) to SP, BFU2015-68354 to THS, Breast Cancer Research Foundation (BCRF-17-008) to JA, AGL2014-52395-C2-2-R to DA, Worldwide Cancer Research, Red Temática de Investigación Cooperativa en Cáncer (RD012/0036/005), Fundación Científica de la Asociación Española contra el Cáncer, and Fundació La Marató TV3. THS was supported by institutional funding (MINECO) through the Centres of Excellence Severo Ochoa award and the CERCA Programme of the Catalan Government, and SS-B, by a Fundació La Caixa fellowship. We thank La Caixa Foundation and Cellex Foundation for provide research facilities and equipment. GV has received funding from the MINECO (a “Juan de la Cierva Incorporation” fellowship; IJCI-2014-20723). SP was a recipient of a Miguel Servet contract (ISCIII/FIS), and AI, JPC-C, LP-G, and GS-B are supported by contracts from Worldwide Cancer Research, Fundació La Marató TV3, Fundació FERO, and a FI Fellowship from the Generalitat de Catalunya, respectively.
dc.format
application/pdf
dc.format
application/pdf
dc.format
application/pdf
dc.format
application/pdf
dc.publisher
Springer Nature
dc.relation
Oncogene;39(1)
dc.relation
https://doi.org/10.1038/s41388-019-0969-1
dc.relation
info:eu-repo/grantAgreement/ES/1PN/2008-2011/PI12%2F01250
dc.relation
info:eu-repo/grantAgreement/ES/2PN/CP08%2F00223
dc.relation
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00253
dc.relation
info:eu-repo/grantAgreement/ES/PE2013-2016/CB16%2F12%2F00449
dc.relation
info:eu-repo/grantAgreement/ES/PE2013-2016/SAF2013-48849-C2-1-R
dc.relation
info:eu-repo/grantAgreement/ES/PE2013-2016/IJCI-2014-20723
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Mama - Càncer - Aspectes genètics
dc.subject
Regulació genètica
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Structures::Chromosome Structures::Chromatin
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::estructuras genéticas::estructuras cromosómicas::cromatina
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica
dc.title
LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
