Metastasis is the major cause of
cancer deaths and control of gene transcription has emerged as a critical contributing factor. RhoA- and RhoC-induced gene transcription via the actin-regulated transcriptional co-activator
megakaryocytic leukemia (MKL) and
serum response factor (SRF) drive
metastasis in
breast cancer and
melanoma. We recently identified a compound,
CCG-1423, which blocks Rho/MKL/SRF-mediated transcription and inhibits PC-3
prostate cancer cell invasion. Here, we undertook a genome-wide expression study in PC-3 cells to explore the mechanism and function of this compound. There was significant overlap in the genes modulated by
CCG-1423 and
Latrunculin B (
Lat B), which blocks the Rho/MKL/SRF pathway by preventing actin polymerization. In contrast, the general transcription inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (
DRB) showed a markedly different pattern. Effects of
CCG-1423 and
Lat B on gene expression correlated with literature studies of MKL knock-down. Gene sets involved in
DNA synthesis and repair, G1/S transition, and apoptosis were modulated by
CCG-1423. It also upregulated genes involved in endoplasmic reticulum stress. Targets of the known Rho target
transcription factor family E2F and genes related to
melanoma progression and
metastasis were strongly suppressed by
CCG-1423. These results confirm the ability of our compound to inhibit expression of numerous Rho/MKL-dependent genes and show effects on stress pathways as well. This suggests a novel approach to targeting aggressive
cancers and
metastasis.