The Galectins as Targets for Cancer Therapeutics

Abstract

The galectins are the most ancient and widely expressed family of glycan-binding protein, and have been found in all metazoans examined to date. Galectins recognise and bind to carbohydrate ligands, specifically those that contain β-galactosides, and it is via these interactions, and through direct protein–protein interactions, that the galectins perform their highly diverse collection of activities. In humans, the galectins are found in both the intracellular and extracellular environments, and have important roles in many aspects of cellular homeostasis, cell signalling, and cell adhesion. Of importance for this project is that most of the functions of galectins, even those involving direct protein–protein interactions, are found to be inhibitable by carbohydrate ligands. Many galectin functions are related to important aspects of tumour progression and cancer, and it has emerged that the galectins are playing many negative roles in disease processes. Some galectins are found to be involved in tumour growth, adhesion, migration, and immune escape, with galectin expression levels in tumour cells often correlating with tumour aggressiveness, metastatic potential, and poor patient prognosis. The most extensively studied members of the galectin family, and for which there exists the most detailed evidence regarding their roles in disease, are galectins -1 and -3. As such, these two proteins have been identified as promising targets for cancer therapy, and are under investigation in this project.