IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52523-y.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    Veneto Institute of Molecular Medicine)

  • Antonio Rosato

    (Veneto Institute of Oncology IOV - IRCCS
    University of Padova)

  • Paola Cogo

    (Pediatric Research Institute “Città della Speranza”
    Udine University)

  • Salvatore Pece

    (European Institute of Oncology IRCCS
    University of Milan)

  • Massimo M. Santoro

    (University of Padova
    Veneto Institute of Molecular Medicine)

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.

Suggested Citation

  • Giovanni Tosi & Alessandro Paoli & Gaia Zuccolotto & Emilia Turco & Manuela Simonato & Daniela Tosoni & Francesco Tucci & Pietro Lugato & Monica Giomo & Nicola Elvassore & Antonio Rosato & Paola Cogo , 2024. "Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52523-y
    DOI: 10.1038/s41467-024-52523-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52523-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52523-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Valeria Capaci & Lorenzo Bascetta & Marco Fantuz & Galina V. Beznoussenko & Roberta Sommaggio & Valeria Cancila & Andrea Bisso & Elena Campaner & Alexander A. Mironov & Jacek R. Wiśniewski & Luisa Ull, 2020. "Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    2. Christina Curtis & Sohrab P. Shah & Suet-Feung Chin & Gulisa Turashvili & Oscar M. Rueda & Mark J. Dunning & Doug Speed & Andy G. Lynch & Shamith Samarajiwa & Yinyin Yuan & Stefan Gräf & Gavin Ha & Gh, 2012. "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups," Nature, Nature, vol. 486(7403), pages 346-352, June.
    3. Lintao Song & Zhihua Liu & Hui-Hui Hu & Ying Yang & Terytty Yang Li & Zhi-Zhong Lin & Jing Ye & Jianing Chen & Xi Huang & Dong-Tai Liu & Jing Zhou & Yiran Shi & Hao Zhao & Changchuan Xie & Lanfen Chen, 2020. "Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    4. Da-Yun Jin & Xuejie Chen & Yizhou Liu & Craig M. Williams & Lars C. Pedersen & Darrel W. Stafford & Jian-Ke Tie, 2023. "A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Kirill Bersuker & Joseph M. Hendricks & Zhipeng Li & Leslie Magtanong & Breanna Ford & Peter H. Tang & Melissa A. Roberts & Bingqi Tong & Thomas J. Maimone & Roberto Zoncu & Michael C. Bassik & Daniel, 2019. "The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis," Nature, Nature, vol. 575(7784), pages 688-692, November.
    6. Sebastian Doll & Florencio Porto Freitas & Ron Shah & Maceler Aldrovandi & Milene Costa Silva & Irina Ingold & Andrea Goya Grocin & Thamara Nishida Xavier da Silva & Elena Panzilius & Christina H. Sch, 2019. "FSP1 is a glutathione-independent ferroptosis suppressor," Nature, Nature, vol. 575(7784), pages 693-698, November.
    7. M. G. Filippone & D. Gaglio & R. Bonfanti & F. A. Tucci & E. Ceccacci & R. Pennisi & M. Bonanomi & G. Jodice & M. Tillhon & F. Montani & G. Bertalot & S. Freddi & M. Vecchi & A. Taglialatela & M. Roma, 2022. "CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    8. Jessalyn M. Ubellacker & Alpaslan Tasdogan & Vijayashree Ramesh & Bo Shen & Evann C. Mitchell & Misty S. Martin-Sandoval & Zhimin Gu & Michael L. McCormick & Alison B. Durham & Douglas R. Spitz & Zhiy, 2020. "Lymph protects metastasizing melanoma cells from ferroptosis," Nature, Nature, vol. 585(7823), pages 113-118, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Pranavi Koppula & Guang Lei & Yilei Zhang & Yuelong Yan & Chao Mao & Lavanya Kondiparthi & Jiejun Shi & Xiaoguang Liu & Amber Horbath & Molina Das & Wei Li & Masha V. Poyurovsky & Kellen Olszewski & B, 2022. "A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Mihee Oh & Seo Young Jang & Ji-Yoon Lee & Jong Woo Kim & Youngae Jung & Jiwoo Kim & Jinho Seo & Tae-Su Han & Eunji Jang & Hye Young Son & Dain Kim & Min Wook Kim & Jin-Sung Park & Kwon-Ho Song & Kyoun, 2023. "The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Wei Yang & Bo Mu & Jing You & Chenyu Tian & Huachao Bin & Zhiqiang Xu & Liting Zhang & Ronggang Ma & Ming Wu & Guo Zhang & Chong Huang & Linli Li & Zhenhua Shao & Lunzhi Dai & Laurent Désaubry & Sheng, 2022. "Non-classical ferroptosis inhibition by a small molecule targeting PHB2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Nathan P. Ward & Sang Jun Yoon & Tyce Flynn & Amanda M. Sherwood & Maddison A. Olley & Juliana Madej & Gina M. DeNicola, 2024. "Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Yun Lv & Chunhui Liang & Qichao Sun & Jing Zhu & Haiyan Xu & Xiaoqing Li & Yao-yao Li & Qihai Wang & Huiqing Yuan & Bo Chu & Deyu Zhu, 2023. "Structural insights into FSP1 catalysis and ferroptosis inhibition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Samya Van Coillie & Emily Van San & Ines Goetschalckx & Bartosz Wiernicki & Banibrata Mukhopadhyay & Wulf Tonnus & Sze Men Choi & Ria Roelandt & Catalina Dumitrascu & Ludwig Lamberts & Geert Dams & Wa, 2022. "Targeting ferroptosis protects against experimental (multi)organ dysfunction and death," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Dadi Jiang & Youming Guo & Tianyu Wang & Liang Wang & Yuelong Yan & Ling Xia & Rakesh Bam & Zhifen Yang & Hyemin Lee & Takao Iwawaki & Boyi Gan & Albert C. Koong, 2024. "IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Juliane Tschuck & Lea Theilacker & Ina Rothenaigner & Stefanie A. I. Weiß & Banu Akdogan & Van Thanh Lam & Constanze Müller & Roman Graf & Stefanie Brandner & Christian Pütz & Tamara Rieder & Philippe, 2023. "Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Bartosz Wiernicki & Sophia Maschalidi & Jonathan Pinney & Sandy Adjemian & Tom Vanden Berghe & Kodi S. Ravichandran & Peter Vandenabeele, 2022. "Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Da-Yun Jin & Xuejie Chen & Yizhou Liu & Craig M. Williams & Lars C. Pedersen & Darrel W. Stafford & Jian-Ke Tie, 2023. "A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Xinyi Shan & Jiahuan Li & Jiahao Liu & Baoli Feng & Ting Zhang & Qian Liu & Huixin Ma & Honghong Wu & Hao Wu, 2023. "Targeting ferroptosis by poly(acrylic) acid coated Mn3O4 nanoparticles alleviates acute liver injury," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Juliane Tschuck & Vidya Padmanabhan Nair & Ana Galhoz & Carole Zaratiegui & Hin-Man Tai & Gabriele Ciceri & Ina Rothenaigner & Jason Tchieu & Brent R. Stockwell & Lorenz Studer & Daphne S. Cabianca & , 2024. "Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    13. Xin Chen & Jun Huang & Chunhua Yu & Jiao Liu & Wanli Gao & Jingbo Li & Xinxin Song & Zhuan Zhou & Changfeng Li & Yangchun Xie & Guido Kroemer & Jinbao Liu & Daolin Tang & Rui Kang, 2022. "A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    14. Aleix Prat & Fara Brasó-Maristany & Olga Martínez-Sáez & Esther Sanfeliu & Youli Xia & Meritxell Bellet & Patricia Galván & Débora Martínez & Tomás Pascual & Mercedes Marín-Aguilera & Anna Rodríguez &, 2023. "Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Liang, Weijuan & Zhang, Qingzhao & Ma, Shuangge, 2024. "Hierarchical false discovery rate control for high-dimensional survival analysis with interactions," Computational Statistics & Data Analysis, Elsevier, vol. 192(C).
    16. Yandi Wu & Tongsheng Huang & Xinghui Li & Conghui Shen & Honglin Ren & Haiping Wang & Teng Wu & Xinlu Fu & Shijie Deng & Ziqi Feng & Shijie Xiong & Hui Li & Saifei Gao & Zhenyu Yang & Fei Gao & Lele D, 2023. "Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Hugh Chen & Scott M. Lundberg & Su-In Lee, 2022. "Explaining a series of models by propagating Shapley values," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Adam C. Weiner & Marc J. Williams & Hongyu Shi & Ignacio Vázquez-García & Sohrab Salehi & Nicole Rusk & Samuel Aparicio & Sohrab P. Shah & Andrew McPherson, 2024. "Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Marco, Nicholas & Şentürk, Damla & Jeste, Shafali & DiStefano, Charlotte C. & Dickinson, Abigail & Telesca, Donatello, 2024. "Flexible regularized estimation in high-dimensional mixed membership models," Computational Statistics & Data Analysis, Elsevier, vol. 194(C).
    20. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52523-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.