ADT increases prostate cancer cell invasion via altering AR/SALL4/SOX2-OCT4 stem cell signaling

Abstract

Abstract Early studies indicated that the androgen-deprivation-therapy with antiandrogen Enzalutamide could increase prostate cancer patients’ survival by an average of 4.8 months. Yet Enz might also have some adverse effects via increasing the PCa cell invasion. Here we found Enz treatment could increase oncogene SALL4 expression to increase the cancer stem cells population that resulted in increasing the PCa cell invasion. Mechanisn dissection revealed that Enz could function via androgen receptor to transcriptionally regulate the SALL4 expression via direct binding to the androgen-response-elements on the SALL4 5'-promoter. The consequences of such Enz/AR/SALL4 axis may then lead to transcriptionally increase the SOX2-OCT4 expression to increase the CSC population to increase the PCa cell invasion. Together, results from multiple in vitro cell lines and in vivo mouse model all conclude that Enz may induce the adverse effect of increasing PCa cell invasion via altering the AR/SALL4/SOX2-OCT4 signaling to increase the CSC population, and targeting this newly identified signaling with small molecule of sh-SALL4 may decrease this adverse effect to further suppress the PCa progression.