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Learn MoreS-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM has been unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated cancer cell lines HepG2 and SKHep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and silenced by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and silences genes in pathways of growth and metastasis that are activated in liver cancer cells. Depletion of two SAM silencing targets similarly reduces cellular transformation and invasiveness. Taken together these data provide a molecular foundation for SAM as an anticancer agent. SOURCE: Wang YanMoshe Szyf McGill University
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