Biomechanical regulation of breast cancer metastasis and progression

Abstract Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investiga...

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Autores principales:	Adrianne Spencer, Andrew D. Sligar, Daniel Chavarria, Jason Lee, Darshil Choksi, Nikita P. Patil, HooWon Lee, Austin P. Veith, William J. Riley, Shubh Desai, Ali Abbaspour, Rohan Singeetham, Aaron B. Baker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a531adafa99e4e2d802cbdaf0a1f6fcc
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spelling	oai:doaj.org-article:a531adafa99e4e2d802cbdaf0a1f6fcc2021-12-02T14:35:40ZBiomechanical regulation of breast cancer metastasis and progression10.1038/s41598-021-89288-z2045-2322https://doaj.org/article/a531adafa99e4e2d802cbdaf0a1f6fcc2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89288-zhttps://doaj.org/toc/2045-2322Abstract Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.Adrianne SpencerAndrew D. SligarDaniel ChavarriaJason LeeDarshil ChoksiNikita P. PatilHooWon LeeAustin P. VeithWilliam J. RileyShubh DesaiAli AbbaspourRohan SingeethamAaron B. BakerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adrianne Spencer Andrew D. Sligar Daniel Chavarria Jason Lee Darshil Choksi Nikita P. Patil HooWon Lee Austin P. Veith William J. Riley Shubh Desai Ali Abbaspour Rohan Singeetham Aaron B. Baker Biomechanical regulation of breast cancer metastasis and progression
description	Abstract Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.
format	article
author	Adrianne Spencer Andrew D. Sligar Daniel Chavarria Jason Lee Darshil Choksi Nikita P. Patil HooWon Lee Austin P. Veith William J. Riley Shubh Desai Ali Abbaspour Rohan Singeetham Aaron B. Baker
author_facet	Adrianne Spencer Andrew D. Sligar Daniel Chavarria Jason Lee Darshil Choksi Nikita P. Patil HooWon Lee Austin P. Veith William J. Riley Shubh Desai Ali Abbaspour Rohan Singeetham Aaron B. Baker
author_sort	Adrianne Spencer
title	Biomechanical regulation of breast cancer metastasis and progression
title_short	Biomechanical regulation of breast cancer metastasis and progression
title_full	Biomechanical regulation of breast cancer metastasis and progression
title_fullStr	Biomechanical regulation of breast cancer metastasis and progression
title_full_unstemmed	Biomechanical regulation of breast cancer metastasis and progression
title_sort	biomechanical regulation of breast cancer metastasis and progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a531adafa99e4e2d802cbdaf0a1f6fcc
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Biomechanical regulation of breast cancer metastasis and progression

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