The Role of Actin Polymerization in Tumor Metastasis
Abstract
Breast cancer is frequently associate with gene amplification of EMS1 or cortactin, a protein that regulates the assembly of filamentous actin (F-actin). Previous studies have demonstrated that overexpression of cortactin results in increase in metastases and invasion of breast tumor cells. The goal of this project is to reveal the biological significance of the interaction of cortactin with phospholipids, which are known to play a critical role in the modulation of cell migration in response to extracellular stimuli. Cortactin binds to a subset of phosphatidylinositides, including phosphatidylinositol 5- phosphoate (PI(5)P), phosphatidylinoistol 4,5 biophosphoate (PI(4,5)P2) and phosphatidylinositol 4-phosphoate (PI(4)P). Interestingly, not all those phospholipids show a similar effect on%the activity of cortactin. While PI(5)P increases the activity of cortactin for actin assembly, PI(4)P inhibits the cortactin mediated actin branching. This data indicates that the activity of cortactin is regulated by different types of membrane phospholipids. In addition, we also utilized small interference RNA to inhibit the expression of cortactin in breast cancer cells. These RNAs inhibit the cortactin expression by more than 80%, impair the actin assembly and reduce the formation of invadopodia. Thus, cortactin is essential for the actin-based invasiveness of tumor cells and modulates actin assembly that is subject to regulation by specific phospholipids.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA420763
Entities
People
- Xi Zhan
Organizations
- American Red Cross