The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer

Abstract

Prostate cancer is the second most common lethal cancer in men worldwide. Despite the fact that the prognosis for patients with localized disease is good, many patients succumb to metastatic disease with the development of resistance to hormone treatments. This is normally termed castration-resistant prostate cancer (CRPC). The development of metastatic, castration-resistant prostate cancer has been associated with epithelial-to-mesenchymal transition (EMT), a process where cancer cells acquire a more mesenchymal phenotype with enhanced migratory potential, invasiveness and elevated resistance to apoptosis. The main event in EMT is the repression of epithelial markers such as E-cadherin and upregulation of mesenchymal markers such as N-cadherin, vimentin and fibronectin. The insulin-like growth factor (IGF) signalling axis is essential for normal development and maintenance of tissues, including that of the prostate, and dysregulation of this pathway contributes to prostate cancer progression and malignant transformation. It is becoming increasingly clear that one of the ways in which the IGF axis impacts upon cancer progression is through promoting EMT. This review will explore the role of EMT in prostate cancer progression with a specific focus on the involvement of the IGF axis and its downstream signalling pathways in regulating EMT in prostate cancer.