Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F17%3A00473151" target="_blank" >RIV/86652036:_____/17:00473151 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/17:00473151 RIV/00216208:11160/17:10372943 RIV/00216208:11310/17:10372943

Result on the web

<a href="http://dx.doi.org/10.18632/oncotarget.14093" target="_blank" >http://dx.doi.org/10.18632/oncotarget.14093</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.14093" target="_blank" >10.18632/oncotarget.14093</a>

Result language

angličtina

Original language name

Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

Original language description

The 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

OncoTarget

ISSN

1949-2553

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

23

Pages from-to

6376-6398

UT code for WoS article

000393289000082

EID of the result in the Scopus database

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