Yi, XinWright, Laura E.Pagnotti, Gabriel M.Uzer, GunesPowell, Katherine M.Wallace, Joseph M.Sankar, UmaRubin, Clinton T.Mohammad, KhalidGuise, Theresa A.Thompson, William R.2021-12-132021-12-132020-11-17Yi, X., Wright, L. E., Pagnotti, G. M., Uzer, G., Powell, K. M., Wallace, J. M., Sankar, U., Rubin, C. T., Mohammad, K., Guise, T. A., & Thompson, W. R. (2020). Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity. Bone Research, 8, 40. https://doi.org/10.1038/s41413-020-00111-32095-4700https://hdl.handle.net/1805/27164Exercise 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.enAttribution 4.0 United Statesbreast cancerbreast cancer cell invasionnucleo-cytoskeletal connectivityArticle