Function of the Alpha6 in Breast Carcinoma
Abstract
Breast carcinoma invasion is a complex process that involves directed migration and localized proteolysis, as well as the survival of cells in foreign tissue. Recent work by our group defined an integrin-mediated mechanism of breast carcinoma invasion that involves the stimulation of carcinoma migration by the dynamic association of alpha 6 beta 4 with F-actin and the activation of a specific signaling pathway by this integrin. Studies carried out during Year 3 of this grant have extended our analysis of the contribution of the alpha 6 beta 4 integrin to breast carcinoma progression significantly. A major finding is that alpha 6 beta 4 is a potent activator of the AKT kinase that maintains the survival of metastatic breast carcinoma cells. Interestingly, this pathway is inhibited by p53, an observation which indicates that the ability of alpha 6 beta 4 to maintain survival will be enhanced in p53-deficient breast carcinomas. We also established that alpha 6 beta 4 regulates the activity of RhoA GTPase that is necessary for the migration of invasive carcinoma cells. The significance of this finding is that it increases our understanding of the signaling pathways that are involved in breast cancer invasion. Indeed, it is widely assumed that such signaling pathways will be the target of the next generation of chemotherapeutic agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA381773
Entities
People
- Arthur M Mercurio
Organizations
- Beth Israel Deaconess Medical Center