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

  1. Luca Tirinato  Is a corresponding author
  2. Maria Grazia Marafioti
  3. Francesca Pagliari  Is a corresponding author
  4. Jeannette Jansen
  5. Ilenia Aversa
  6. Rachel Hanley
  7. Clelia Nisticò
  8. Daniel Garcia-Calderón
  9. Geraldine Genard
  10. Joana Filipa Guerreiro
  11. Francesco Saverio Costanzo
  12. Joao Seco  Is a corresponding author
  1. Magna Graecia University, Italy
  2. German Cancer Research Center, Germany
  3. University of Lisbon, Portugal
  4. DKFZ - German Cancer Research Center, Germany

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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. All Source data files have been provided.

Article and author information

Author details

  1. Luca Tirinato

    Magna Graecia University, Catanzaro, Italy
    For correspondence
    tirinato@unicz.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9826-2129
  2. Maria Grazia Marafioti

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Francesca Pagliari

    German Cancer Research Center, Heidelberg, Germany
    For correspondence
    f.pagliari@dkfz.de
    Competing interests
    The authors declare that no competing interests exist.
  4. Jeannette Jansen

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8625-3978
  5. Ilenia Aversa

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Rachel Hanley

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2627-1146
  7. Clelia Nisticò

    Magna Graecia University, Catanzaro, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0787-9527
  8. Daniel Garcia-Calderón

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Geraldine Genard

    German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9495-0335
  10. Joana Filipa Guerreiro

    University of Lisbon, Lisboa, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1960-603X
  11. Francesco Saverio Costanzo

    Magna Graecia University, Catanzaro, Italy
    Competing interests
    The authors declare that no competing interests exist.
  12. Joao Seco

    DKFZ - German Cancer Research Center, Heidelberg, Germany
    For correspondence
    j.seco@dkfz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9458-2202

Funding

AIRC (800924)

  • Luca Tirinato

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wafik S El-Deiry, Brown University, United States

Publication history

  1. Preprint posted: May 13, 2021 (view preprint)
  2. Received: August 12, 2021
  3. Accepted: August 25, 2021
  4. Accepted Manuscript published: September 9, 2021 (version 1)
  5. Accepted Manuscript updated: September 14, 2021 (version 2)
  6. Version of Record published: October 7, 2021 (version 3)

Copyright

© 2021, Tirinato et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Luca Tirinato
  2. Maria Grazia Marafioti
  3. Francesca Pagliari
  4. Jeannette Jansen
  5. Ilenia Aversa
  6. Rachel Hanley
  7. Clelia Nisticò
  8. Daniel Garcia-Calderón
  9. Geraldine Genard
  10. Joana Filipa Guerreiro
  11. Francesco Saverio Costanzo
  12. Joao Seco
(2021)
Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance
eLife 10:e72943.
https://doi.org/10.7554/eLife.72943

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