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

Filipe, EC; Velayuthar, S; Philp, A; Nobis, M; Latham, SL; Parker, AL; Murphy, KJ; Wyllie, K; Major, GS; Contreras, O; Mok, ETY; Enriquez, RF; McGowan, S; Feher, K; Quek, L-E; Hancock, SE; Yam, M; Tran, E; Setargew, YFI; Skhinas, JN; Chitty, JL; Phimmachanh, M; Han, JZR; Cadell, AL; Papanicolaou, M; Mahmodi, H; Kiedik, B; Junankar, S; Ross, SE; Lam, N; Coulson, R; Yang, J; Zaratzian, A; Da Silva, AM; Tayao, M; Chin, IL; Cazet, A; Kansara, M; Segara, D; Parker, A; Hoy, AJ; Harvey, RP; Bogdanovic, O; Timpson, P; Croucher, DR; Lim, E; Swarbrick, A; Holst, J; Turner, N; Choi, YS; Kabakova, IV; Philp, A; Cox, TR

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

Filipe, EC Velayuthar, S Philp, A Nobis, M Latham, SL Parker, AL Murphy, KJ Wyllie, K Major, GS Contreras, O Mok, ETY Enriquez, RF McGowan, S Feher, K Quek, L-E Hancock, SE Yam, M Tran, E Setargew, YFI Skhinas, JN Chitty, JL Phimmachanh, M Han, JZR Cadell, AL Papanicolaou, M Mahmodi, H Kiedik, B Junankar, S Ross, SE Lam, N Coulson, R Yang, J Zaratzian, A Da Silva, AM Tayao, M Chin, IL Cazet, A Kansara, M Segara, D Parker, A Hoy, AJ Harvey, RP Bogdanovic, O Timpson, P Croucher, DR Lim, E Swarbrick, A Holst, J Turner, N Choi, YS Kabakova, IV Philp, A Cox, TR

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Adv Sci (Weinh), 2024, 11, (23), pp. e2307963
Issue Date:: 2024-06

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Field	Value	Language
dc.contributor.author	Filipe, EC
dc.contributor.author	Velayuthar, S
dc.contributor.author	Philp, A
dc.contributor.author	Nobis, M
dc.contributor.author	Latham, SL
dc.contributor.author	Parker, AL
dc.contributor.author	Murphy, KJ
dc.contributor.author	Wyllie, K
dc.contributor.author	Major, GS
dc.contributor.author	Contreras, O
dc.contributor.author	Mok, ETY
dc.contributor.author	Enriquez, RF
dc.contributor.author	McGowan, S
dc.contributor.author	Feher, K
dc.contributor.author	Quek, L-E
dc.contributor.author	Hancock, SE
dc.contributor.author	Yam, M
dc.contributor.author	Tran, E
dc.contributor.author	Setargew, YFI
dc.contributor.author	Skhinas, JN
dc.contributor.author	Chitty, JL
dc.contributor.author	Phimmachanh, M
dc.contributor.author	Han, JZR
dc.contributor.author	Cadell, AL
dc.contributor.author	Papanicolaou, M
dc.contributor.author	Mahmodi, H
dc.contributor.author	Kiedik, B
dc.contributor.author	Junankar, S
dc.contributor.author	Ross, SE
dc.contributor.author	Lam, N
dc.contributor.author	Coulson, R
dc.contributor.author	Yang, J
dc.contributor.author	Zaratzian, A
dc.contributor.author	Da Silva, AM
dc.contributor.author	Tayao, M
dc.contributor.author	Chin, IL
dc.contributor.author	Cazet, A
dc.contributor.author	Kansara, M
dc.contributor.author	Segara, D
dc.contributor.author	Parker, A
dc.contributor.author	Hoy, AJ
dc.contributor.author	Harvey, RP
dc.contributor.author	Bogdanovic, O
dc.contributor.author	Timpson, P
dc.contributor.author	Croucher, DR
dc.contributor.author	Lim, E
dc.contributor.author	Swarbrick, A
dc.contributor.author	Holst, J
dc.contributor.author	Turner, N
dc.contributor.author	Choi, YS
dc.contributor.author	Kabakova, IV
dc.contributor.author	Philp, A
dc.contributor.author	Cox, TR
dc.date.accessioned	2025-01-02T03:51:35Z
dc.date.available	2025-01-02T03:51:35Z
dc.date.issued	2024-06
dc.identifier.citation	Adv Sci (Weinh), 2024, 11, (23), pp. e2307963
dc.identifier.issn	2198-3844
dc.identifier.issn	2198-3844
dc.identifier.uri	http://hdl.handle.net/10453/182792
dc.description.abstract	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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation	http://purl.org/au-research/grants/arc/CE230100006
dc.relation.ispartof	Adv Sci (Weinh)
dc.relation.isbasedon	10.1002/advs.202307963
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Mice
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Biomechanical Phenomena
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Neoplasm Metastasis
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Female
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Biomechanical Phenomena
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Fatty Acids
dc.subject.mesh	Mice
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Animals
dc.subject.mesh	Biomechanical Phenomena
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Neoplasm Metastasis
dc.title	Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	Germany
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)/Institute of Biomedical Materials and Devices (IBMD) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-01-02T03:51:31Z
pubs.issue	23
pubs.publication-status	Published
pubs.volume	11
utslib.citation.issue	23

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/182792