Analysis of the Role of Cortactin in Tumor Cell Invasion
Abstract
Cortactin is an actin cytoskeleton associated protein, frequently amplified and overexpressed along with the chromosome 11q13 in breast cancer, and acts as a prominent substrate of protein tyrosine kinase Src. We have hypothesized that cortactin plays a role in tumor progression by promoting metastasis. To test this hypothesis, we conducted a series of experiments aimed at characterizing the effects of cortactin and its mutant with a defect in tyrosine phosphorylation on cell motility in vitro and metastasis in vivo. These studies have eventually led to following conclusions: (1) cortactin is primarily implicated in actin cytoskeleton reorganization rather than DNA synthesis; (2) overexpression of wild type cortactin can increase cell motility and cell shape changes in response to growth factors and reactive oxygen species in a tyrosine phosphorylation dependent manner; (3) introduction of a cortactin mutant deficient in tyrosine phosphorylation can effectively inhibit cell motility and cell shape changes and depress tumor metastasis in vivo; and (4), the primary biochemical function of cortactin is to modulate actin polymerization by regulating the activity of Arp2/3 complex, a key machinery of actin polymerization. Our studies provide first evidence for the role of actin polymerization in tumor invasion and indicate a novel approach to suppress metastasis by targeting at actin polymerization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398342
Entities
People
- Xi Zhan