IGF-IR, Cell Adhesion and Metastasis
Abstract
The insulin-like growth factor I receptor (IGF-IR) is a multifunctional tyrosine kinase that has been implicated in breast cancer. Current evidence suggests an important role of the IGF-!R in the growth and survival of ER-positive primary breast tumors. However, the function of the IGF-IR in breast cancer metastasis is unknown. Previously we have shown that IGF-I modulates cell-cell and cell-substrate adhesion in breast cancer cells. Consequently, we proposed to investigate the molecular mechanism of IGF-IR-stimulated cell adhesion, and the role of IGF-IR overexpression in breast metastasis. We demonstrated that the IGF-IR promotes E-cadherin-dependent cell-cell adhesion and interacts with the elements of E-cadherin adhesion complex. IGF-IR overexpression or stimulation of cells with IGF-I improved the expression of one of the E-cadherin-associated proteins, ZO- 1. This was paralleled by augmented binding of the IGF-lR to ZO- I and to ZO-l-associated-alpha-catenin and actin. In parallel, we pursued IGF-IR function in E-cadherin negative metastatic breast cancer cells. We demonstrated that in this cellular context, IGF-I has no growth or adhesion function, but it is necessary to stimulate cell motility. The IGF-I-induced motility was mediated through PI-3 and p38 kinases, and was inhibited by the activation of ERKl/ERK2 kinases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA388878
Entities
People
- Ewa Surmacz
Organizations
- Thomas Jefferson University