Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer

Giovanni Tosi, Alessandro Paoli, Gaia Zuccolotto, Emilia Turco, Manuela Simonato, Daniela Tosoni, Francesco Tucci, Pietro Lugato, Monica Giomo, Nicola Elvassore, Antonio Rosato, Paola Cogo, Salvatore Pece and Massimo M. Santoro ()
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Giovanni Tosi: University of Padova
Alessandro Paoli: University of Padova
Gaia Zuccolotto: Veneto Institute of Oncology IOV - IRCCS
Emilia Turco: University of Turin
Manuela Simonato: Pediatric Research Institute “Città della Speranza”
Daniela Tosoni: European Institute of Oncology IRCCS
Francesco Tucci: European Institute of Oncology IRCCS
Pietro Lugato: University of Padova
Monica Giomo: University of Padova
Nicola Elvassore: University of Padova
Antonio Rosato: Veneto Institute of Oncology IOV - IRCCS
Paola Cogo: Pediatric Research Institute “Città della Speranza”
Salvatore Pece: European Institute of Oncology IRCCS
Massimo M. Santoro: University of Padova

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: Abstract CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.

Date: 2024
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DOI: 10.1038/s41467-024-52523-y

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