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dc.contributor.authorRychtarcikova, Zuzana
dc.contributor.authorLettlova, Sandra
dc.contributor.authorTomkova, Veronika
dc.contributor.authorKorenkova, Vlasta
dc.contributor.authorLangerova, Lucie
dc.contributor.authorSimonova, Ekaterina
dc.contributor.authorZjablovskaja, Polina
dc.contributor.authorAlberich-Jorda, Meritxell
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorTruksa, Jaroslav
dc.date.accessioned2020-02-17T02:36:42Z
dc.date.available2020-02-17T02:36:42Z
dc.date.issued2017
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.14093
dc.identifier.urihttp://hdl.handle.net/10072/391560
dc.description.abstractThe importance of iron in the growth and progression of tumors has been widely documented. In this report, we show that tumor-initiating cells (TICs), represented by spheres derived from the MCF7 cell line, exhibit higher intracellular labile iron pool, mitochondrial iron accumulation and are more susceptible to iron chelation. TICs also show activation of the IRP/IRE system, leading to higher iron uptake and decrease in iron storage, suggesting that level of properly assembled cytosolic iron-sulfur clusters (FeS) is reduced. This finding is confirmed by lower enzymatic activity of aconitase and FeS cluster biogenesis enzymes, as well as lower levels of reduced glutathione, implying reduced FeS clusters synthesis/utilization in TICs. Importantly, we have identified specific gene signature related to iron metabolism consisting of genes regulating iron uptake, mitochondrial FeS cluster biogenesis and hypoxic response (ABCB10, ACO1, CYBRD1, EPAS1, GLRX5, HEPH, HFE, IREB2, QSOX1 and TFRC). Principal component analysis based on this signature is able to distinguish TICs from cancer cells in vitro and also Leukemia-initiating cells (LICs) from non-LICs in the mouse model of acute promyelocytic leukemia (APL). Majority of the described changes were also recapitulated in an alternative model represented by MCF7 cells resistant to tamoxifen (TAMR) that exhibit features of TICs. Our findings point to the critical importance of redox balance and iron metabolism-related genes and proteins in the context of cancer and TICs that could be potentially used for cancer diagnostics or therapy.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherImpact Journals, LLC
dc.relation.ispartofpagefrom6376
dc.relation.ispartofpageto6398
dc.relation.ispartofissue4
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume8
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode1112
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsOncology
dc.subject.keywordsCell Biology
dc.subject.keywordstumor-initiating cells
dc.titleTumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationRychtarcikova, Z; Lettlova, S; Tomkova, V; Korenkova, V; Langerova, L; Simonova, E; Zjablovskaja, P; Alberich-Jorda, M; Neuzil, J; Truksa, J, Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism, Oncotarget, 2017, 8 (4), pp. 6376-6398
dcterms.dateAccepted2016-11-30
dcterms.licensehttp://creativecommons.org/licenses/by/3.0/
dc.date.updated2020-02-17T02:34:07Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2016 Rychtarcikova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorNeuzil, Jiri


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