| Literature DB >> 31462706 |
J P Cebrià-Costa1, L Pascual-Reguant1, A Gonzalez-Perez2, G Serra-Bardenys1, J Querol1, M Cosín1, G Verde1,3, R A Cigliano4, W Sanseverino4, S Segura-Bayona2, A Iturbide5, D Andreu6, P Nuciforo1, C Bernado-Morales1,7, V Rodilla1, J Arribas1,7,8,9, J Yelamos10, A Garcia de Herreros6,10, T H Stracker2, S Peiró11.
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.Entities:
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Year: 2019 PMID： 31462706 PMCID： PMC6937214 DOI： 10.1038/s41388-019-0969-1
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867