Journal Article

DKFZ-2021-02007

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance.

Tirinato, L. (First author)DKFZ* ; Marafioti, M. G. (First author)DKFZ* ; Pagliari, F. (First author)DKFZ* ; Jansen, J.DKFZ* ; Aversa, I.DKFZ* ; Hanley, R.DKFZ* ; Nisticò, C.DKFZ* ; Garcia-Calderón, D.DKFZ* ; Genard, G.DKFZ* ; Guerreiro, J. F. ; Costanzo, F. S. ; Seco, J. (Last author)DKFZ*

2021
eLife Sciences Publications Cambridge

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Please use a persistent id in citations: doi:10.7554/eLife.72943

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.

Keyword(s): cancer biology ; human

Note: #EA:E041#LA:E041#

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Contributing Institute(s):

1. E041 Medizinische Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2021

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