biostudies-literatureDarash-Yahana MNIGMS NIH HHS10890-5https://www.ebi.ac.uk/biostudies/studies/S-EPMC5047192biostudies-literatureUnknown113(39)Iron-sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the Proceedings of the National Academy of Sciences of the United States of AmericaBreast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters.PMC5047192R01 GM101467Sohn YSJennings PAPikarsky EGeiger TNechushtai RSong LLu MKarmi ODarash-Yahana MMittler RPozniak YTamir SOnuchic JNBai FfalseBreast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters.Iron-sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the 2016-01-01T00:00:00Z2016 Sep2026-04-07T18:01:09.876Z2019-03-27T02:25:42ZS-EPMC50471922762143910.1073/pnas.1612736113