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- Title
Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity.
- Authors
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.
- Abstract
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.
- Subjects
BREAST cancer diagnosis; CANCER invasiveness; OSTEOCLASTS; CELL communication; CELL differentiation
- Publication
Bone Research, 2020, Vol 8, Issue 1, pN.PAG
- ISSN
2095-4700
- Publication type
Article
- DOI
10.1038/s41413-020-00111-3