LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

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 can...

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Detalles Bibliográficos
Autores: Cebrià i Costa, Joan Pau, 1989-, Pascual-Reguant, Laura, 1990-, Gonzalez-Perez, Abel, Serra Bardenys, Gemma, 1992-, Querol, J., Cosín Tomàs, Marta, Verde, Gaetano, Cigliano, Riccardo Aiese, Sanseverino, Walter, Segura-Bayona, Sandra, Iturbide Martínez de Albéniz, Ane, 1989-, Andreu Martínez, David, Nuciforo, Paolo G., Bernado-Morales, C., Rodilla, Verónica, Arribas, Joaquín, Yélamos López, José, García de Herreros, Antonio, Stracker, Travis, Peiró Sales, Sandra
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44004
Acceso en línea:http://hdl.handle.net/10230/44004
http://dx.doi.org/10.1038/s41388-019-0969-1
Access Level:acceso abierto
Palabra clave:Mama -- Càncer -- Aspectes genètics
Mama -- Càncer -- Tractament
Descripción
Sumario: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.

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