期刊
ONCOGENE
卷 39, 期 1, 页码 79-121出版社
SPRINGERNATURE
DOI: 10.1038/s41388-019-0969-1
关键词
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资金
- Instituto de Salud Carlos III (ISCIII) FIS/FEDER [PI12/01250, CP08/00223, PI16/00253, CB16/12/00449]
- MINECO [SAF201348849-C2-1-R]
- Breast Cancer Research Foundation [BCRF-17-008]
- Worldwide Cancer Research
- Red Tematica de Investigacion Cooperativa en Cancer [RD012/0036/005]
- Fundacion Cientifica de la Asociacion Espanola contra el Cancer
- Fundacio La Marato TV3
- institutional funding (MINECO) through the Centres of Excellence Severo Ochoa award
- CERCA Programme of the Catalan Government
- Fundacio La Caixa fellowship
- MINECO (Juan de la Cierva Incorporation fellowship) [IJCI-2014-20723]
- Miguel Servet contract (ISCIII/FIS)
- Fundacio FERO
- FI Fellowship from the Generalitat de Catalunya
- [BFU2015-68354]
- [AGL2014-52395-C2-2-R]
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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