Figure 3.

(A) Dilazep suppresses GATA2-driven signaling in PC cells. We compared, via GSEA, the transcriptional footprint of dilazep (50 µM for 48 h) with that of GATA2 siRNA in LNCaP, Abl, and MDVR cells. In each cell line, genes downregulated by GATA2 siRNA were strongly enriched among the genes suppressed by dilazep, while genes upregulated by GATA2 siRNA were strongly enriched among the genes induced by dilazep in the same cell line. This provides evidence that dilazep indeed suppresses that GATA2 transcriptional program, in both androgen-dependent and castration-resistant PC cells. (B) Dilazep suppresses the metastatic program of PC cells. We compared, via GSEA, our dilazep-derived signatures in LNCaP, Abl, and MDVR cells to a signature derived from genes differentially expressed between metastatic CRPC and primary, hormone-naïve PC patient specimens. We found that genes preferentially expressed in metastatic CRPC tissues were strongly suppressed by dilazep in all three cell lines tested, while genes downregulated in metastatic CRPC tissues were strongly enriched among the genes induced by dilazep, supporting that dilazep suppresses the metastatic program of PC cells. Moreover, we found that dilazep suppressed, in all three lines tested, a recently described MYC/RAS co-activation signature (META-16) (Arriaga et al. 2020) that is associated with prostate cancer metastasis. A full color version of this figure is available at https://doi.org/10.1530/ERC-21-0085.