Hedgehog-Gli pathway integrates epithelial-mesenchymal transition and stemness properties in prostate cancer cells

Cancer stem cells (CSCs) exhibit stem-like cell properties and play a critical role in cancer initiation, development, progression and therapeutic resistance. The epithelial–mesenchymal transition (EMT) endows cells with migratory and invasive properties, and is also a key driving force for promoting cancer progression. It is reported that EMT is closely associated with CSCs, but the detailed mechanism remains unknown. In this study, we investigated the relationship between EMT and CSCs in prostate cancer and its detailed mechanism using the ARCaPE cell model. We found that compared with the epithelial-like ARCaPE cells, the mesenchymal-like ARCaPM cells showed increased migration capacity, expression of mesenchymal markers and CSC markers, as well as self-renewal capacity. In addition, ARCaPM cells showed higher expression of transcription factor Gli, a mediator of the Hedgehog pathway. Gli inhibitor GANT-61 could inhibit EMT and stemness properties of ARCaPM cells. Our findings indicated that the Hedgehog–Gli pathway integrates EMT and stemness properties in prostate cancer cells, providing new insights into clarifying the potential mechanisms of prostate cancer progression.