Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis
Version of Record online: 19 SEP 2002
Copyright © 2002 Wiley-Liss, Inc.
Microscopy Research and Technique
Special Issue: Histology and Cell Biology of Breast Cancer—Part I
Volume 59, Issue 1, pages 58–67, 1 October 2002
How to Cite
Nakamoto, M. and Bergemann, A. D. (2002), Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis. Microsc. Res. Tech., 59: 58–67. doi: 10.1002/jemt.10177
- Issue online: 19 SEP 2002
- Version of Record online: 19 SEP 2002
- Manuscript Accepted: 28 SEP 2001
- Manuscript Received: 25 JUL 2001
- Whitehall Foundation
- March of Dimes
The Eph family of receptor tyrosine kinases and their cell-presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small-cell lung and gastrointestinal cancers, melanomas, and neuroblastomas. In particular, one Eph family member, EphA2, is overexpressed in many cancers, including 40% of breast cancers. EphA2 can also transform breast epithelial cells in vitro to display properties commonly associated with the development of metastasis. Remarkably, the oncogenic properties of EphA2 contravene traditional dogma with regard to the oncogenic properties of a growth factor and its receptor tyrosine kinase: while stimulation of EphA2 by its ligand (ephrin-A1) results in EphA2 autophosphorylation, the stimulation reverses the oncogenic transformation. As will be discussed in this review, the apparent dependence of oncogenicity on the dephosphorylated state of EphA2 most probably reflects the unique nature of Eph signaling. In particular, oncogenecity may depend on the capacity of unactivated EphA2 to interact with a variety of signaling molecules. As well as acting in oncogenic transformation, a growing body of evidence supports the importance of the concerted actions of ephrins and Eph molecules in tumor angiogenesis. Genetic studies, using targeted mutagenesis in mice, reveal that ephrin-B1, ephrin-B2, and EphB4 are essential for the normal morphogenesis of the embryonic vasculature into a sophisticated network of arteries, veins, and capillaries. Initial studies indicate that these molecules are also angiogenic in tumors, and as such represent important new targets for the development of chemotherapeutic treatments. Microsc. Res. Tech. 59:58–67, 2002. © 2002 Wiley-Liss, Inc.