Cancer Cell Stiffening Via CoQ and UBIAD1 Regulates ECM Signaling and Ferroptosis in Breast Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Sep 18

PMID 39294175

Authors

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

Massimo M Santoro

Affiliations

Soon will be listed here.

Abstract

CoQ (Coenzyme Q) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ 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 CoQ and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ 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 CoQ and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.

Citing Articles

The Ubiquitous and Multifaceted Coenzyme Q.

Tiano L, Navas P Antioxidants (Basel). 2024; 13(10).

PMID: 39456514 PMC: 11504101. DOI: 10.3390/antiox13101261.

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