Mechanotransduction from the ECM to the genome: Are the pieces now in place?
Article first published online: 1 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Special Issue: Nuclear Microenvironments in Cancer Series
Volume 104, Issue 6, pages 1964–1987, 15 August 2008
How to Cite
Gieni, R. S. and Hendzel, M. J. (2008), Mechanotransduction from the ECM to the genome: Are the pieces now in place?. J. Cell. Biochem., 104: 1964–1987. doi: 10.1002/jcb.21364
- Issue published online: 22 JUL 2008
- Article first published online: 1 JUN 2007
- Manuscript Accepted: 12 MAR 2007
- Manuscript Received: 8 MAR 2007
- Canadian Institutes of Health Research
- National Cancer Institute of Canada
- cell nucleus;
A multitude of biochemical signaling processes have been characterized that affect gene expression and cellular activity. However, living cells often need to integrate biochemical signals with mechanical information from their microenvironment as they respond. In fact, the signals received by shape alone can dictate cell fate. This mechanotrasduction of information is powerful, eliciting proliferation, differentiation, or apoptosis in a manner dependent upon the extent of physical deformation. The cells internal “prestressed” structure and its “hardwired” interaction with the extra-cellular matrix (ECM) appear to confer this ability to filter biochemical signals and decide between divergent cell functions influenced by the nature of signals from the mechanical environment. In some instances mechanical signaling through the tissue microenvironment has been shown to be dominant over genomic defects, imparting a normal phenotype on cells that otherwise have transforming genetic lesions. This mechanical control of phenotype is postulated to have a central role in embryogenesis, tissue physiology as well as the pathology of a wide variety of diseases, including cancer. We will briefly review studies showing physical continuity between the external cellular microenvironment and the interior of the cell nucleus. Newly characterized structures, termed nuclear envelope lamina spanning complexes (NELSC), and their interactions will be described as part of a model for mechanical transduction of extracellular cues from the ECM to the genome. J. Cell. Biochem. 104: 1964–1987, 2008. © 2007 Wiley-Liss, Inc.