Matches in SemOpenAlex for { <https://semopenalex.org/work/W3202968128> ?p ?o ?g. }
- W3202968128 abstract "Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including hexokinase-2 and pyruvate dehydrogenase. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at hexokinase-2 and pyruvate dehydrogenase, accompanied by enhanced glycolysis and TCA cycle metabolism. AMPKα-2, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas." @default.
- W3202968128 created "2021-10-11" @default.
- W3202968128 creator A5001293585 @default.
- W3202968128 creator A5002271939 @default.
- W3202968128 creator A5003311852 @default.
- W3202968128 creator A5008395370 @default.
- W3202968128 creator A5011298500 @default.
- W3202968128 creator A5012006306 @default.
- W3202968128 creator A5012070305 @default.
- W3202968128 creator A5012407631 @default.
- W3202968128 creator A5012955659 @default.
- W3202968128 creator A5015186722 @default.
- W3202968128 creator A5019140507 @default.
- W3202968128 creator A5020491193 @default.
- W3202968128 creator A5022278084 @default.
- W3202968128 creator A5022692329 @default.
- W3202968128 creator A5026659386 @default.
- W3202968128 creator A5027926846 @default.
- W3202968128 creator A5038035447 @default.
- W3202968128 creator A5038715165 @default.
- W3202968128 creator A5039059536 @default.
- W3202968128 creator A5039496084 @default.
- W3202968128 creator A5040936511 @default.
- W3202968128 creator A5041096535 @default.
- W3202968128 creator A5041171133 @default.
- W3202968128 creator A5044366354 @default.
- W3202968128 creator A5050535456 @default.
- W3202968128 creator A5051824786 @default.
- W3202968128 creator A5052967210 @default.
- W3202968128 creator A5059000453 @default.
- W3202968128 creator A5060449174 @default.
- W3202968128 creator A5062386210 @default.
- W3202968128 creator A5064694236 @default.
- W3202968128 creator A5067013860 @default.
- W3202968128 creator A5067479835 @default.
- W3202968128 creator A5073211182 @default.
- W3202968128 creator A5074425984 @default.
- W3202968128 creator A5075671062 @default.
- W3202968128 creator A5077346536 @default.
- W3202968128 creator A5079064470 @default.
- W3202968128 creator A5080133701 @default.
- W3202968128 creator A5080146061 @default.
- W3202968128 creator A5083767613 @default.
- W3202968128 creator A5083834388 @default.
- W3202968128 creator A5085736600 @default.
- W3202968128 creator A5089653376 @default.
- W3202968128 date "2021-10-06" @default.
- W3202968128 modified "2023-10-16" @default.
- W3202968128 title "Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas" @default.
- W3202968128 cites W1949037014 @default.
- W3202968128 cites W1976979641 @default.
- W3202968128 cites W2022899908 @default.
- W3202968128 cites W2044874695 @default.
- W3202968128 cites W2051921450 @default.
- W3202968128 cites W2061059838 @default.
- W3202968128 cites W2113432767 @default.
- W3202968128 cites W2140048538 @default.
- W3202968128 cites W2149135409 @default.
- W3202968128 cites W2314376783 @default.
- W3202968128 cites W2460811760 @default.
- W3202968128 cites W2549992612 @default.
- W3202968128 cites W2592743985 @default.
- W3202968128 cites W2593125811 @default.
- W3202968128 cites W2606835938 @default.
- W3202968128 cites W2714552381 @default.
- W3202968128 cites W2737623654 @default.
- W3202968128 cites W2771357379 @default.
- W3202968128 cites W2780843582 @default.
- W3202968128 cites W2807973758 @default.
- W3202968128 cites W2896808622 @default.
- W3202968128 cites W2924177262 @default.
- W3202968128 cites W2925940295 @default.
- W3202968128 cites W2946243434 @default.
- W3202968128 cites W2954090867 @default.
- W3202968128 cites W2955366030 @default.
- W3202968128 cites W2970574493 @default.
- W3202968128 cites W2982884868 @default.
- W3202968128 cites W2991430679 @default.
- W3202968128 cites W2999105571 @default.
- W3202968128 cites W3011594395 @default.
- W3202968128 cites W3027987756 @default.
- W3202968128 cites W3043795706 @default.
- W3202968128 cites W3044625941 @default.
- W3202968128 cites W3048694655 @default.
- W3202968128 cites W3048798848 @default.
- W3202968128 cites W3092520164 @default.
- W3202968128 doi "https://doi.org/10.1126/scitranslmed.abc0497" @default.
- W3202968128 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34613815" @default.
- W3202968128 hasPublicationYear "2021" @default.
- W3202968128 type Work @default.
- W3202968128 sameAs 3202968128 @default.
- W3202968128 citedByCount "25" @default.
- W3202968128 countsByYear W32029681282021 @default.
- W3202968128 countsByYear W32029681282022 @default.
- W3202968128 countsByYear W32029681282023 @default.
- W3202968128 crossrefType "journal-article" @default.
- W3202968128 hasAuthorship W3202968128A5001293585 @default.
- W3202968128 hasAuthorship W3202968128A5002271939 @default.
- W3202968128 hasAuthorship W3202968128A5003311852 @default.
- W3202968128 hasAuthorship W3202968128A5008395370 @default.