Importantly, PAK4 reversed nine of E2-mediated target genes expression by using RNA-seq analysis, including CLSTN2, IL1R1, FOXM1, TNFRSF11B, CCNG2, TNS3, ABCG1, SMAD3, and SERPINA3. Further studies will examine whether the target genes are involved in modulation of breast-bone metastasis in breast cancer by nPAK4 with E2 stimulation. The gene discussed is SMAD3; the disease is breast cancer.