Disrupting Cu trafficking as a potential therapy for cancer

Zena Qasem, Matic Pavlin, Ida Ritacco, Matan Y. Avivi, Shelly Meron, Melanie Hirsch, Yulia Shenberger, Lada Gevorkyan-Airapetov, Alessandra Magistrato, Sharon Ruthstein

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Copper ions play a crucial role in various cellular biological processes. However, these copper ions can also lead to toxicity when their concentration is not controlled by a sophisticated copper-trafficking system. Copper dys-homeostasis has been linked to a variety of diseases, including neurodegeneration and cancer. Therefore, manipulating Cu-trafficking to trigger selective cancer cell death may be a viable strategy with therapeutic benefit. By exploiting combined in silico and experimental strategies, we identified small peptides able to bind Atox1 and metal-binding domains 3-4 of ATP7B proteins. We found that these peptides reduced the proliferation of cancer cells owing to increased cellular copper ions concentration. These outcomes support the idea of harming copper trafficking as an opportunity for devising novel anti-cancer therapies.

Original languageEnglish
Article number1011294
JournalFrontiers in Molecular Biosciences
Volume9
DOIs
StatePublished - 10 Oct 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Qasem, Pavlin, Ritacco, Avivi, Meron, Hirsch, Shenberger, Gevorkyan-Airapetov, Magistrato and Ruthstein.

Funding

This research was funded by the ERC-STG grant no. 754365 awarded to SR. AM thanks the Italian Association for Cancer Research (AIRC) (IG grant 24514) for financial support. MP thanks the Slovenian Research Agency (ARRS) (research core funding P2-0152) for financial support.

FundersFunder number
ERC-STG754365
Javna Agencija za Raziskovalno Dejavnost RSP2-0152
Associazione Italiana per la Ricerca sul Cancro24514

    Keywords

    • ATP7B
    • Atox1
    • cancer therapy
    • copper metabolism
    • peptide design

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