The Role of Focal Adhesion Kinase and CAS in Integrin-Mediated Signaling on Distinct Forms of Laminin-5
Abstract
Breast cancer develops in two stages The first, hyperproliferation, causes primary tumors and is rarely lethal. In the second stage, malignancy, tumor cells penetrate the surrounding basement membrane layer of extracellular matrix proteins and migrate into adjacent tissues where they form secondary, metastatic tumors. The defining characteristics of malignant cancer cells are hyperproliferation and an aggressively migratory phenotype. We have two models whereby an immortal, non-metastatic breast epithelial cell can be induced to constitutively migrate on its preferred adhesive substrate, laminin-5. The first model is by direct activation of the laminin-5 integrin receptor alpha 3 beta 1 with a beta-1-integrin activating antibody. The second is by modification of laminin-5 by specific proteolytic cleavage, an event known to occur in cancerous tissues. This project's goal is to analyze the contribution of the signaling molecules FAK and CAS to the cascade that induces migration of breast cells on laminin-5. In the first phase of this research we determined that FAK and CAS are phosphorylated upon binding of breast cells to laminin-5, and that phosphorylation is enhanced when these cells are bound to the cleaved form of laminin-5. The focus of the current work is to analyze these molecules in the model of direct integrin activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396637
Entities
People
- Janice L. Huff
Organizations
- University of Nevada, Las Vegas