Genetic and signaling pathway regulations of tumor-initiating cells of the prostate

Here we review current literature on genetic and signaling pathway regulators of tumor initiating cells in prostate cancer. While we emphasize the consequence of PTEN loss and PI3K/AKT activation in prostate cancer initiating cells, we also assess the importance of other signaling regulators, including RAS/MAPK, WNT/β-catenin, MYC, NKX3.1 and p53 on these cells.Importantly, we stress how these factors alone, or in collaboration, alter tumor initiating cell/cancer stem cell function and consequently, phenotypes in in vivo prostate cancer models.Our review also highlights the understanding of how genetic pathway alteration influences cancer initiation by way of lineage tracing or cell type specific disruption.Functional similarities and differences of how tumor suppressor loss impacts human prostate cancer are also addressed, where appropriate.Finally, we touch on outstanding questions that future experimentation will hopefully address.