Regulation of Actin-Myosin Cytoskeletal Changes Involved in Cancer Metastasis
Abstract
This research is aimed to define the molecular events mediating tumor cell migration during metastasis. Although myosin is required for motility, how force is generated to initiate and maintain directed movement of non-muscle cells remains poorly understood. We have two approaches to elucidate myosin-based motility with high spatial and temporal resolution. Green fluorescent protein (GFP) tagged myosin II regulatory light chain (RLC) has allowed us to follow the reorganization of the myosin network during motility. Since RLC is regulated by multiple signals, further understanding of the signaling events cannot be accomplished without dynamic spatio-temporal dissection of the pathways. To accomplish this, we have generated a novel biosensor that allows us to simultaneously monitor the subcellular localization of myosin light chain kinase (MLCK) and its state of activation, we have characterized how myosin is regulated at various subcellular regions during cell motility. To establish a baseline for studies of breast cancer cells, we used PTK-2 epithelial cells to understand the role of myosin at the leading edge of motile cells. The MLCK-FIP biosensor has highlighted myosin function unlikely to be controlled. Our initial efforts have established the necessary techniques and the basic principles of MLCK-mediated non-muscle myosin regulation to characterize the fundamental differences in the acto-myosin cytoskeleton in non-invasive and the highly aggressive tumor breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396662
Entities
People
- Teng-leong Chew
Organizations
- Northwestern University