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We began analyzing https://www.nature.com/articles/s41467-019-09277-9, but it redirected us to https://www.nature.com/articles/s41467-019-09277-9. The analysis below is for the second page.

Title[redir]:
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis | Nature Communications
Description:
Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers. Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.

Matching Content Categories {📚}

  • Science
  • Education
  • Telecommunications

Content Management System {📝}

What CMS is doi.org built with?

Custom-built

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Traffic Estimate {📈}

What is the average monthly size of doi.org audience?

🏙️ Massive Traffic: 50M - 100M visitors per month


Based on our best estimate, this website will receive around 98,426,998 visitors per month in the current month.

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Not all websites focus on profit; some are designed to educate, connect people, or share useful tools. People create websites for numerous reasons. And this could be one such example. Doi.org has a secret sauce for making money, but we can't detect it yet.

Keywords {🔍}

cells, cell, ferroptosis, cancer, article, fig, scholar, supplementary, google, data, cas, sensitivity, gpx, lipid, analysis, hifα, cccs, hilpda, nature, experiments, expression, carcinoma, genes, lines, ccrcc, protein, susceptibility, viability, levels, epas, renal, clearcell, rsl, treated, gene, crispr, screening, clear, death, pathway, results, ccc, representative, media, including, metabolic, treatment, sgrna, condition, state,

Topics {✒️}

crispr/cas9-mediated genome editing crispr/cas9-mediated genome-editing /remontoire-pac/ctrp-reference/tree/master/auc] nature portfolio gov/programs/ctd2/data-portal] gov/pub/ocg-dcc/ctd2/broad/] privacy policy iron-dependent cell-death pathway15 irdye 800cw goat-anti-rabbit hif-2α/hif-1β protein levels advertising epas1-targeting sgrna-expressing 786-o-cas9 index sequence identification p62-keap1-nrf2 pathway protects sensitized hif-2α-null cells 2 × 150 bp paired-end configuration hif-2α/gpx4 double knockouts reporting summary barely impacted sfa/mufa-lipids hif-2α-regulated molecular program previous chip-seq data tailed mann–whitney–wilcoxon test kidney cancer research papillary renal-cell carcinoma lipidomics data analysis identified hif-2α-dependent genes hif-2α-dependent genes identified high-score g0s2-targeting sgrna reprints dynamic nature von hippel-lindau protein homologous pnpla-binding motif saturated/monounsaturated fatty acyl metastatic renal-cell carcinoma vinyl ether-linked pe-plasmalogens von hippel-lindau gene personal research funds pufa-lipid-enriched cell state genome-wide crispr screen lc-ms system comprising mann–whitney–wilcoxon tests ovarian clear-cell carcinoma supplementary data tables hif-1/2α mediates sensitivity rna-seq data analysis hif-2α/hif-1β sequence-independent g0s2-targeting shrnas hif-2α-depletion induced gpx4-dependent cell state author information authors

Questions {❓}

Schema {🗺️}

WebPage:
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         headline:A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
         description:Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers. Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.
         datePublished:2019-04-08T00:00:00Z
         dateModified:2019-04-08T00:00:00Z
         pageStart:1
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         keywords:
            Cancer metabolism
            Cell death
            Lipidomics
            Ovarian cancer
            Renal cell carcinoma
            Science
            Humanities and Social Sciences
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      headline:A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
      description:Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers. Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.
      datePublished:2019-04-08T00:00:00Z
      dateModified:2019-04-08T00:00:00Z
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      license:http://creativecommons.org/licenses/by/4.0/
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         Cancer metabolism
         Cell death
         Lipidomics
         Ovarian cancer
         Renal cell carcinoma
         Science
         Humanities and Social Sciences
         multidisciplinary
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