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@ARTICLE{Tirinato:170556,
author = {L. Tirinato$^*$ and M. G. Marafioti$^*$ and F. Pagliari$^*$
and J. Jansen$^*$ and I. Aversa$^*$ and R. Hanley$^*$ and C.
Nisticò$^*$ and D. Garcia-Calderón$^*$ and G. Genard$^*$
and J. F. Guerreiro and F. S. Costanzo and J. Seco$^*$},
title = {{L}ipid droplets and ferritin heavy chain: a devilish
liaison in human cancer cell radioresistance.},
journal = {eLife},
volume = {10},
issn = {2050-084X},
address = {Cambridge},
publisher = {eLife Sciences Publications},
reportid = {DKFZ-2021-02007},
pages = {e72943},
year = {2021},
note = {#EA:E041#LA:E041#},
abstract = {Although much progress has been made in cancer treatment,
the molecular mechanisms underlying cancer radioresistance
(RR) as well as the biological signatures of radioresistant
cancer cells still need to be clarified. In this regard, we
discovered that breast, bladder, lung, neuroglioma and
prostate 6 Gy X-ray resistant cancer cells were
characterized by an increase of Lipid Droplet (LD) number
and that the cells containing highest LDs showed the highest
clonogenic potential after irradiation. Moreover, we
observed that LD content was tightly connected with the iron
metabolism and in particular with the presence of the
ferritin heavy chain (FTH1). In fact, breast and lung cancer
cells silenced for the FTH1 gene showed a reduction in the
LD numbers and, by consequence, became radiosensitive. FTH1
overexpression as well as iron-chelating treatment by
Deferoxamine were able to restore the LD amount and RR.
Overall, these results provide evidence of a novel mechanism
behind RR in which LDs and FTH1 are tightly connected to
each other, a synergistic effect which might be worth deeply
investigating in order to make cancer cells more
radiosensitive and improve the efficacy of radiation
treatments.},
keywords = {cancer biology (Other) / human (Other)},
cin = {E041},
ddc = {600},
cid = {I:(DE-He78)E041-20160331},
pnm = {315 - Bildgebung und Radioonkologie (POF4-315)},
pid = {G:(DE-HGF)POF4-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34499029},
doi = {10.7554/eLife.72943},
url = {https://inrepo02.dkfz.de/record/170556},
}