Cargando…

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

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 prostat...

Descripción completa

Detalles Bibliográficos
Autores principales: Tirinato, Luca, Marafioti, Maria Grazia, Pagliari, Francesca, Jansen, Jeannette, Aversa, Ilenia, Hanley, Rachel, Nisticò, Clelia, Garcia-Calderón, Daniel, Genard, Geraldine, Guerreiro, Joana Filipa, Costanzo, Francesco Saverio, Seco, Joao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497056/
https://www.ncbi.nlm.nih.gov/pubmed/34499029
http://dx.doi.org/10.7554/eLife.72943
_version_ 1784579873825619968
author Tirinato, Luca
Marafioti, Maria Grazia
Pagliari, Francesca
Jansen, Jeannette
Aversa, Ilenia
Hanley, Rachel
Nisticò, Clelia
Garcia-Calderón, Daniel
Genard, Geraldine
Guerreiro, Joana Filipa
Costanzo, Francesco Saverio
Seco, Joao
author_facet Tirinato, Luca
Marafioti, Maria Grazia
Pagliari, Francesca
Jansen, Jeannette
Aversa, Ilenia
Hanley, Rachel
Nisticò, Clelia
Garcia-Calderón, Daniel
Genard, Geraldine
Guerreiro, Joana Filipa
Costanzo, Francesco Saverio
Seco, Joao
author_sort Tirinato, Luca
collection PubMed
description 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 that might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.
format Online
Article
Text
id pubmed-8497056
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-84970562021-10-08 Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance Tirinato, Luca Marafioti, Maria Grazia Pagliari, Francesca Jansen, Jeannette Aversa, Ilenia Hanley, Rachel Nisticò, Clelia Garcia-Calderón, Daniel Genard, Geraldine Guerreiro, Joana Filipa Costanzo, Francesco Saverio Seco, Joao eLife Cancer Biology 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 that might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments. eLife Sciences Publications, Ltd 2021-09-09 /pmc/articles/PMC8497056/ /pubmed/34499029 http://dx.doi.org/10.7554/eLife.72943 Text en © 2021, Tirinato et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Tirinato, Luca
Marafioti, Maria Grazia
Pagliari, Francesca
Jansen, Jeannette
Aversa, Ilenia
Hanley, Rachel
Nisticò, Clelia
Garcia-Calderón, Daniel
Genard, Geraldine
Guerreiro, Joana Filipa
Costanzo, Francesco Saverio
Seco, Joao
Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title_full Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title_fullStr Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title_full_unstemmed Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title_short Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
title_sort lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497056/
https://www.ncbi.nlm.nih.gov/pubmed/34499029
http://dx.doi.org/10.7554/eLife.72943
work_keys_str_mv AT tirinatoluca lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT marafiotimariagrazia lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT pagliarifrancesca lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT jansenjeannette lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT aversailenia lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT hanleyrachel lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT nisticoclelia lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT garciacalderondaniel lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT genardgeraldine lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT guerreirojoanafilipa lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT costanzofrancescosaverio lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance
AT secojoao lipiddropletsandferritinheavychainadevilishliaisoninhumancancercellradioresistance