{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alvarez SW"],"funding":["NIAID NIH HHS","NCI NIH HHS","NIH HHS","NIGMS NIH HHS"],"pagination":["639-643"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5808442"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["551(7682)"],"pubmed_abstract":["Environmental nutrient levels impact cancer cell metabolism, resulting in context-dependent gene essentiality. Here, using loss-of-function screening based on RNA interference, we show that environmental oxygen levels are a major driver of differential essentiality between in vitro model systems and in vivo tumours. Above the 3-8% oxygen concentration typical of most tissues, we find that cancer cells depend on high levels of the iron-sulfur cluster biosynthetic enzyme NFS1. Mammary or subcutaneous tumours grow despite suppression of NFS1, whereas metastatic or primary lung tumours do not. Consistent with a role in surviving the high oxygen environment of incipient lung tumours, NFS1 lies in a region of genomic amplification present in lung adenocarcinoma and is most highly expressed in we"],"journal":["Nature"],"pubmed_title":["NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis."],"pmcid":["PMC5808442"],"funding_grant_id":["K22 CA193660","S10 OD010584-01","K99 CA168940","R01 CA129105","T32 GM115313","T32 AI007389","R01 CA103866","R37 AI047389","S10 OD010584","T32 GM007308","S10 OD016304","S10 OD018338","CA168940","P30 CA016087","R00 CA168940"],"pubmed_authors":["Papagiannakopoulos T","Sabatini DM","Birsoy K","Possemato R","Sviderskiy VO","Adams S","Moreira AL","Alvarez SW","Terzi EM"],"additional_accession":[]},"is_claimable":false,"name":"NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis.","description":"Environmental nutrient levels impact cancer cell metabolism, resulting in context-dependent gene essentiality. Here, using loss-of-function screening based on RNA interference, we show that environmental oxygen levels are a major driver of differential essentiality between in vitro model systems and in vivo tumours. Above the 3-8% oxygen concentration typical of most tissues, we find that cancer cells depend on high levels of the iron-sulfur cluster biosynthetic enzyme NFS1. Mammary or subcutaneous tumours grow despite suppression of NFS1, whereas metastatic or primary lung tumours do not. Consistent with a role in surviving the high oxygen environment of incipient lung tumours, NFS1 lies in a region of genomic amplification present in lung adenocarcinoma and is most highly expressed in we","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Nov","modification":"2025-04-04T14:48:44.788Z","creation":"2019-03-26T23:38:23Z"},"accession":"S-EPMC5808442","cross_references":{"pubmed":["29168506"],"doi":["10.1038/nature24637"]}}