Epithelial-to-mesenchymal transition in breast cancer: a role for insulin-like growth factor I and insulin-like growth factor–binding protein 3?

Abstract

Hanna A Zielinska,1 Amit Bahl,2 Jeff MP Holly,1 Claire M Perks1 1IGFs and Metabolic Endocrinology Group, School of Clinical Sciences, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK; 2Department of Clinical Oncology, Bristol Haematology and Oncology Centre, University Hospitals Bristol, Bristol, UK Abstract: Evidence indicates that for most human cancers the problem is not that gene mutations occur but is more dependent upon how the body deals with damaged cells. It has been estimated that only about 1% of human cancers can be accounted for by unmistakable hereditary cancer syndromes, only up to 5% can be accounted for due to high-penetrance, single-gene mutations, and in total only 5%–15% of all cancers may have a major genetic component. The predominant contribution to the causation of most sporadic cancers is considered to be environmental factors contributing between 58% and 82% toward different cancers. A nutritionally poor lifestyle is associated with increased risk of many cancers, including those of the breast. As nutrition, energy balance, macronutrient composition of the diet, and physical activity levels are major determinants of insulin-like growth factor (IGF-I) bioactivity, it has been proposed that, at least in part, these increases in cancer risk and progression may be mediated by alterations in the IGF axis, related to nutritional lifestyle. Localized breast cancer is a manageable disease, and death from breast cancer predominantly occurs due to the development of metastatic disease as treatment becomes more complicated with poorer outcomes. In recent years, epithelial-to-mesenchymal transition has emerged as an important contributor to breast cancer progression and malignant transformation resulting in tumor cells with increased potential for migration and invasion. Furthermore, accumulating evidence suggests a strong link between components of the IGF pathway, epithelial-to-mesenchymal transition, and breast cancer mortality. Here, we highlight some recent studies highlighting the relationship between IGFs, IGF-binding protein 3, and epithelial-to-mesenchymal transition. Keywords: IGF-I, IGFBP-3, EMT, breast cancer