Deciphering protein-DNA interactions of KISS1 with transcription factors through molecular docking, molecular dynamics simulations, and gene expression analysis.

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 KISS1 and key transcription factors (TFs) involved in metastasis: SP1, CDX2, FLI1, GATA2, NMYC, and HDAC2. TFs were identified via TFLink, modelled using SWISS-MODEL, and docked with KISS1-DNA using HADDOCK. CDX2 showed the strongest binding (HADDOCK score: -144.2; buried surface area: 2526.5 Å2), followed by HDAC2, GATA2, NMYC, SP1, and FLI1. Molecular dynamics simulations (150 ns) revealed stable complexes for SP1, NMYC, and CDX2 with low RMSD (2.1-2.7 Å), compact Rg (∼21.0 Å), 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 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, KISS1 demonstrates strong potential as a transcriptional regulator and therapeutic agent against TNBC metastasis.

• Publication year

  2025

• Venue

  Journal of Biomolecular Structure and Dynamics

• Publication date

  2025-09-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/07391102.2025.2553344PMID 40910466
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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