Function of the Alpha6 in Breast Carcinoma.
Abstract
The oc6beta4 integrin promotes breast carcinoma invasion by its activation of a phosphoinositide 3-OH (P13 K)signaling pathway (Shaw et al., Cell 91:949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that oc6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by oc6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon oc6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or gated' by cAMP and our results reveal that a critical function of oc6beta4 is to suppress the intracellular cAMP concentration by increasing the activity of a rolipram-sensitive, cAMP-specific phosphodiesterase (PDE). This PDE activity is essential for lamellae formation, chemotactic migration and invasion based on data obtained with PDE inhibitors. Although P13-K and cAMP-specific PDE activities are both required to promote lamellae formation and chemotactic migration, our data indicate that they are components of distinct signaling pathways. The essence of our findings is that oc6beta4 stimulates the chemotactic migration of breast carcinoma cells through its ability to influence key signaling events that underlie this critical component of breast carcinoma invasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA358071
Entities
People
- Arthur M Mercurio
Organizations
- Beth Israel Deaconess Medical Center