Role of RAC GTPases in Tumor Mobility and Metastasis.
Abstract
Integrins act as signal transducers that regulate cell adhesion, spreading and motility on the extracellular matrix. Small GTP-binding proteins become activated in response to integrin ligation. Although members of the Rho family of small GTP-binding proteins control organization of the actin cytoskeleton, little is known about how they impact integrin-dependent cellular events on the ECM. Evidence is provided that cells transfected with Tiami (I lymphomainvasion and metastasis), a Rac activator, showed a 3A fold enhanced cell motility on collagen I, while cells expressing dominant negative Rac Tl7N failed to migrate in response to Tiami. Overexpression of dominant positive small GTP-binding protein Rac did not significantly alter cell motility on collagen alone, however, its expression synergized with Raf kinase to activate MAP kinase and promote cell motility. Treatment of cells with a MAP kinase kinase (MEK) inhibitor, PD98059, and wortamanin, an inhibitor of phosphatidylinositide-3-kinase (PI3K), completely blocked Tiami-induced cell motility. These results delineate roles of MAP kinase and PI3K in the regulation of integrin-mediated cell motility by the small GTP-binding protein Rac.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA337864
Entities
People
- Jie Leng
Organizations
- Scripps Research