Notch signaling in the prostate: critical roles during development and in the hallmarks of prostate cancer biology

Abstract

Purpose: This review aims to summarize the evidence that Notch signaling is associated with prostate development, tumorigenesis and prostate tumor progression. Methods: Studies in PubMed database were searched using the keywords of Notch signaling, prostate development and prostate cancer. Relevant literatures were identified and summarized. Results: The Notch pathway plays an important role in determining cell fate, proliferation, differentiation and apoptosis. Recent findings have highlighted the involvement of Notch signaling in prostate development and in the maintenance of adult prostate homeostasis. Aberrant Notch expression in tissues leads to dysregulation of Notch functions and promotes various neoplasms, including prostate cancer. High expression of Notch has been implicated in prostate cancer, and its expression increases with higher cancer grade. However, the precise role of Notch in prostate cancer has yet to be clearly defined. The roles of Notch either as an oncogene or tumor suppressor in prostate cancer hallmarks such as cell proliferation, apoptosis and anoikis, hypoxia, migration and invasion, angiogenesis as well as the correlation with metastasis are therefore discussed. Conclusions: Notch signaling is a complicated signaling pathway in modulating prostate development and prostate cancer. Understanding and manipulating Notch signaling could therefore be of potential therapeutic value in combating prostate cancer.