Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

biomechanics breast cancer extracellular matrix metabolism metastasis

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
11 Apr 2024
Historique:
revised: 11 03 2024
received: 23 10 2023
medline: 11 4 2024
pubmed: 11 4 2024
entrez: 11 4 2024
Statut: aheadofprint

Résumé

In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

Identifiants

pubmed: 38602451
doi: 10.1002/advs.202307963
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2307963

Subventions

Organisme : Australian Research Council
Organisme : Perpetual
Organisme : National Heart Foundation of Australia
Organisme : Cancer Council NSW
Organisme : National Health and Medical Research Council
Organisme : Australian Government Research Training Program

Informations de copyright

© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.

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Auteurs

Elysse C Filipe (EC)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Sipiththa Velayuthar (S)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Ashleigh Philp (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Centenary Institute, Camperdown, NSW, 2050, Australia.

Max Nobis (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Sharissa L Latham (SL)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Amelia L Parker (AL)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Kendelle J Murphy (KJ)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Kaitlin Wyllie (K)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Gretel S Major (GS)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Osvaldo Contreras (O)

School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.

Ellie T Y Mok (ETY)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Ronaldo F Enriquez (RF)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Suzanne McGowan (S)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Kristen Feher (K)

South Australian immunoGENomics Cancer Institute (SAiGENCI), Adelaide, SA, 5005, Australia.

Lake-Ee Quek (LE)

School of Mathematics and Statistics, Charles Perkins Centre, University of Sydney, Sydney, 2050, Australia.

Sarah E Hancock (SE)

Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.
School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia.

Michelle Yam (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Emmi Tran (E)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Yordanos F I Setargew (YFI)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Joanna N Skhinas (JN)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Jessica L Chitty (JL)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Monica Phimmachanh (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Jeremy Z R Han (JZR)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Antonia L Cadell (AL)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Michael Papanicolaou (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Life Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Hadi Mahmodi (H)

School of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Beata Kiedik (B)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Simon Junankar (S)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Samuel E Ross (SE)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Natasha Lam (N)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Rhiannon Coulson (R)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Jessica Yang (J)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Anaiis Zaratzian (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Andrew M Da Silva (AM)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Michael Tayao (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.

Ian L Chin (IL)

School of Human Sciences, University of Western Australia, Crawley, WA, 6009, Australia.

Aurélie Cazet (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Maya Kansara (M)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Davendra Segara (D)

St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia.

Andrew Parker (A)

School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Department of Pathology, St. Vincent's Hospital, Sydney, 2010, Australia.

Andrew J Hoy (AJ)

School of Medical Sciences, Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2050, Australia.

Richard P Harvey (RP)

School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.

Ozren Bogdanovic (O)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, 2033, Australia.

Paul Timpson (P)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

David R Croucher (DR)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Elgene Lim (E)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Alexander Swarbrick (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Jeff Holst (J)

School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia.

Nigel Turner (N)

Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.
School of Biomedical Sciences, UNSW Sydney, Sydney, 2033, Australia.

Yu Suk Choi (YS)

School of Human Sciences, University of Western Australia, Crawley, WA, 6009, Australia.

Irina V Kabakova (IV)

School of Mathematical and Physical Sciences, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Andrew Philp (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.
Biology of Ageing Laboratory and Centre for Healthy Ageing, Centenary Institute, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia.
School of Sport, Exercise and Rehabilitation Sciences, University of Technology Sydney, Ultimo, NSW, 2007, Australia.

Thomas R Cox (TR)

Cancer Ecosystems Program, Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, Sydney, 2010, Australia.

Classifications MeSH