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Cebrià-Costa, J.P.* ; Pascual-Reguant, L.* ; Gonzalez-Perez, A.* ; Serra-Bardenys, G.* ; Querol, J.* ; Cosín, M.* ; Verde, G.* ; Cigliano, R.A.* ; Sanseverino, W.* ; Segura-Bayona, S.* ; Iturbide Martinez De Albeniz, A. ; Andreu, D.* ; Nuciforo, P.* ; Bernado-Morales, C.* ; Rodilla, V.* ; Arribas, J.* ; Yelamos, J.* ; de Herreros, A.G.* ; Stracker, T.H.* ; Peiró, S.*

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

Oncogene 39, 79-121 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Oxidase-like 2; Double-strand Breaks; To-mesenchymal Transition; Dna-damage Response; Lysyl Oxidase; Genomic Instability; E-cadherin; Loxl2; Expression; Transcription
ISSN (print) / ISBN 0950-9232
e-ISSN 0950-9232
Journal Oncogene
Quellenangaben Volume: 39, Issue: 1, Pages: 79-121 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed