Cargando…

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity

Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict...

Descripción completa

Detalles Bibliográficos
Autores principales: Yi, Xin, Wright, Laura E., Pagnotti, Gabriel M., Uzer, Gunes, Powell, Katherine M., Wallace, Joseph M., Sankar, Uma, Rubin, Clinton T., Mohammad, Khalid, Guise, Theresa A., Thompson, William R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673025/
https://www.ncbi.nlm.nih.gov/pubmed/33298883
http://dx.doi.org/10.1038/s41413-020-00111-3
_version_ 1783611251238109184
author Yi, Xin
Wright, Laura E.
Pagnotti, Gabriel M.
Uzer, Gunes
Powell, Katherine M.
Wallace, Joseph M.
Sankar, Uma
Rubin, Clinton T.
Mohammad, Khalid
Guise, Theresa A.
Thompson, William R.
author_facet Yi, Xin
Wright, Laura E.
Pagnotti, Gabriel M.
Uzer, Gunes
Powell, Katherine M.
Wallace, Joseph M.
Sankar, Uma
Rubin, Clinton T.
Mohammad, Khalid
Guise, Theresa A.
Thompson, William R.
author_sort Yi, Xin
collection PubMed
description Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.
format Online
Article
Text
id pubmed-7673025
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-76730252020-11-20 Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity Yi, Xin Wright, Laura E. Pagnotti, Gabriel M. Uzer, Gunes Powell, Katherine M. Wallace, Joseph M. Sankar, Uma Rubin, Clinton T. Mohammad, Khalid Guise, Theresa A. Thompson, William R. Bone Res Article Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling. Nature Publishing Group UK 2020-11-17 /pmc/articles/PMC7673025/ /pubmed/33298883 http://dx.doi.org/10.1038/s41413-020-00111-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yi, Xin
Wright, Laura E.
Pagnotti, Gabriel M.
Uzer, Gunes
Powell, Katherine M.
Wallace, Joseph M.
Sankar, Uma
Rubin, Clinton T.
Mohammad, Khalid
Guise, Theresa A.
Thompson, William R.
Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title_full Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title_fullStr Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title_full_unstemmed Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title_short Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
title_sort mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673025/
https://www.ncbi.nlm.nih.gov/pubmed/33298883
http://dx.doi.org/10.1038/s41413-020-00111-3
work_keys_str_mv AT yixin mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT wrightlaurae mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT pagnottigabrielm mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT uzergunes mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT powellkatherinem mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT wallacejosephm mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT sankaruma mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT rubinclintont mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT mohammadkhalid mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT guisetheresaa mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity
AT thompsonwilliamr mechanicalsuppressionofbreastcancercellinvasionandparacrinesignalingtoosteoclastsrequiresnucleocytoskeletalconnectivity