In our myxofibrosarcoma models, PAK1 nuclear entry significantly increased STAT5B transcriptional output to enhance CSF2 transactivation, as evidenced by the direct interaction between PAK1 and STAT5B, the CSF2 promoter occupancy by STAT5B/PAK1, and the negative impact on CSF2 promoter luciferase activity imposed by the STAT5B binding site-deleted construct and siSTAT5. Notably, pCMV6-PAK1Y3F significantly downregulated CSF2 mRNA and protein, and both siCSF2 and neutralizing anti-CSF2 effectively abolished PAK1-induced HUVEV network formation. This evidence concerns the gene CSF2 and myxofibrosarcoma.