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标题：Linkage of methionine addiction, histone lysine hypermethylation, and malignancy
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作者：Jun Yamamoto ; Sachiko Inubushi ; Qinghong Han 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-17
DOI：10.1016/j.isci.2022.104162
语种：English
出版社：Elsevier
摘要：SummaryMethionine addiction, found in all types of cancer investigated, is because of the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we compared the histone H3 lysine-methylation status and degree of malignancy between methionine-addicted cancer cells and their isogenic methionine-independent revertants, selected by their growth in low concentration of methionine. The methionine-independent revertans can grow on low levels of methionine or independently of exogenous methionine using methionine precursors, as do normal cells. In the methionine-independent revertants, the excess levels of trimethylated histone H3 lysine marks found in the methionine-addicted parental cancer cells were reduced or lost, and their tumorigenicity and experimental metastatic potential in nude mice were also highly reduced. Methionine addiction of cancer is linked with malignancy and hypermethylation of histone H3 lysines. The results of the present study thus provide a unique framework to further understand a fundamental basis of malignancy.Graphical abstractDisplay OmittedHighlights•Methionine(MET)-independent revertants were selected from MET-addicted cancer cells•MET-independent revertants had greatly reduced malignancy•MET-independent revertants have lost or reduced methylation of H3 lysine marks•MET addiction, malignancy, and hypermethylated H3 lysine marks are linkedBiological sciences; Molecular biology; Cell biology; Cancer