Scientists studied how the protein KISS1 (and its short piece kisspeptin‑10) interacts with DNA‑binding proteins that drive cancer spread. In lab breast‑cancer cells, kisspeptin‑10 at about 100 nM changed the activity of several transcription factors, boosting some that may suppress metastasis and lowering others that promote it. The work shows a possible anti‑cancer effect but does not give any human‑usable dosing or safety info.

Metastasis is a key hallmark of cancer aggressiveness, particularly in triple-negative breast cancer (TNBC), which lacks effective targeted therapies. Kisspeptin-1 (KISS1), a known metastasis suppressor is emerging as a potential therapeutic modulator. This study investigates the structural and regulatory interactions between <i>KISS1</i> and key transcription factors (TFs) involved in metastasis: SP1, CDX2, FLI1, GATA2, NMYC, and HDAC2. TFs were identified <i>via</i> TFLink, modelled using SWISS-MODEL, and docked with <i>KISS1</i>-DNA using HADDOCK. CDX2 showed the strongest binding (HADDOCK score: -144.2; buried surface area: 2526.5&#x2009;&#xc5;²), followed by HDAC2, GATA2, NMYC, SP1, and FLI1. Molecular dynamics simulations (150&#x2009;ns) revealed stable complexes for SP1, NMYC, and CDX2 with low RMSD (2.1-2.7&#x2009;&#xc5;), compact Rg (&#x223c;21.0&#x2009;&#xc5;), and stable hydrogen bonding (5-9 bonds). In contrast, FLI1 and GATA2 showed greater flexibility and unstable interactions. Experimental validation in MDA-MB-231 cells treated with Kisspeptin-10 (IC₅₀: 100.21&#x2009;nM) showed upregulation of SP1, NMYC, CDX2, and GATA2, and downregulation of FLI1 and HDAC2. These findings suggest KISS1 selectively modulates transcriptional activity toward anti-metastatic signaling. Overall, <i>KISS1</i> demonstrates strong potential as a transcriptional regulator and therapeutic agent against TNBC metastasis.