Cell Adhesion, Signaling and Myosin in Breast Cancer
Abstract
Cytoskeletal remodeling is crucial in many cellular events, including the adhesion, spreading and motility of breast cancer cells. The Rho family of small GTPases (Rho, Rac and Cdc42) are signal transducers that regulate cytoskeletun dynamics. Our studies have shown that Rac1 is important fur cell spreading, a biological process in which the cyloskeleton is highly active. Rac activity is high only during early stages of spreading. The activity of p-21 activating kinase (PAK), an effector molecule for Rac and Cdc42 GTPases, Is also high only during the early stages of spreading. Overexpression of catalytically active PAK inhibits cell spreading and decreases myosin phosphorylation. Myosin is the cytoskeletal protein which provides the force generating ability to the actin cytoskeleton. We showed this effect of PAK was due to phosphorylation and inhibition of myosin light chain kinase (MLCK), the enzyme that phosphorylates the light chain of myosin II. We also found a second target of PAK in be LIM kinase, which regulates actin depolymerization. Our recent work has focused on the observation that PAKs are highly active in certain breast cancer cell lines. We have attempted to determine why PAK activity is elevated in these cells, whether downstream mediator activity is similarly increased, and how this contributes to overall breast cancer motility.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398096
Entities
People
- Elisabeth Jeanclos
- Luraynne Sanders
Organizations
- Scripps Research