Function of Etk in Growth Factor Receptor Signaling to Integrins in Breast Cancer
Abstract
The central hypothesis in this IDEA Award is that increased integrin-mediated adhesiveness and migration of breast cancer cells in response to stimulation by the growth factor heregulinBeta (HRGBeta) is mediated by phosphoinositide 3-OH kinase (PI 3-K)-dependent activation and membrane recruitment of the novel Tec family tyrosine kinase Etk. Results obtained during this project support this hypothesis, as have demonstrated that: 1) HRGBeta stimulation results in PI 3-K-dependent tyrosine phosphorylation of endogenous and transfected Etk; 2) the PH domain of Etk binds to the major phospholipid produced by active PI 3-K; and 3) modulation of Etk activity and/or expression alters breast cancer cell migration and HRGBeta-induced increases in integrin-dependent adhesion to extracellular matrix proteins. We also demonstrated a clear association between the migratory and metastatic potential of breast cancer cell lines with expression of Etk. Thus, these results have identified a novel function for the Etk tyrosine kinase in regulating growth factor signaling to integrins in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA416688
Entities
People
- Yoji Shimizu
Organizations
- University of Minnesota