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Cellular senescence is a stable cell-cycle arrest,which can be induced by over expressio no fonco genes,genetic mutatios and chemo the rapy treatment.In senescence,methylation of histone H3K9 is an essential mechanism,in which the danymic steady state of methylation and demethylation plays important roles.Here,we show that H3K9-active demethylasescould disable senescence and permit direct transformation under oncogenic Ras.Accordingly,we find that tumor cells growth is dependent on high H3K9 demethylase activity,and to respond to targeted inhibitor therapy in vitro and in vivo.