Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 17, 2020
- Source ID
- 10.1038/s41413-020-00111-3
Entities
People
- Clinton T. Rubin
- Gabriel M. Pagnotti
- Gunes Uzer
- Joseph M. Wallace
- Katherine M. Powell
- Khalid Mohammad
- Laura E. Wright
- Theresa A. Guise
- Uma Sankar
- William R Thompson
- Xin Yi
Organizations
- Foundation for the National Institutes of Health
- United States Department of Defense