PlexinD1 drives the lineage plasticity in advanced prostate cancer

PlexinD1 is an axon guidance molecule which is upregulated in neuroendocrine prostate cancer (PC). In order to better understand its role in mediating the development and disease progression in PC, we performed the RNA-seq in PC cells in lack of or with enforced PlexinD1 expression comparing to the control cells. We compared the gene expression profile and conducted downstream pathway analysis. Our data dememstrated that PlexinD1 regulates the cell lineage in castration-resistant PC by activating Gli1 signaling. To investigate the function of PlexinD1, we knocked down PlexinD1 in C4-2B ENZR and 22Rv1 cells and overexpress PlexinD1 in LNCaP cells using lentivirues. Two parental prostate cancer cell lines, C4-2B ENZR and LNCaP, were also included to characterize the gene signature of enzalutamide-resistant prostate cancer cells. Differentially exrepressed genes and pathway regulated by PlexinD1 were further analyzed using R, IPA and GSEA software.