Related Experiment Video

Updated: Sep 9, 2025

Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
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Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders

Published on: September 4, 2011

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Deciphering protein-DNA interactions of KISS1 with transcription factors through molecular docking, molecular

Hetvi Shah1, Pranav Pillai2, Lipi Buch2

  • 1TREE Lab, Department of Biomedical and Life Sciences, School of Science, Navrachana University, Vadodara, India.

Journal of Biomolecular Structure & Dynamics
|September 5, 2025
PubMed

Insights

Kisspeptin-1 (KISS1) modulates key transcription factors to suppress metastasis in triple-negative breast cancer (TNBC). This study reveals KISS1

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Structural Biology

Background:

  • Metastasis is a critical challenge in triple-negative breast cancer (TNBC), lacking targeted therapies.
  • Kisspeptin-1 (KISS1) is a known metastasis suppressor with therapeutic potential.
  • Understanding KISS1's interaction with transcription factors (TFs) is crucial for TNBC treatment.

Purpose of the Study:

  • Investigate structural and regulatory interactions between KISS1 and metastasis-associated TFs.
  • Determine the binding affinity and stability of KISS1-TF complexes.
  • Validate the effect of KISS1 on TF expression in TNBC cells.

Main Methods:

  • TF identification using TFLink and molecular modeling with SWISS-MODEL.
  • Protein-DNA docking simulations using HADDOCK to assess binding.
  • Molecular dynamics simulations (150 ns) to analyze complex stability.
  • Experimental validation in MDA-MB-231 cells treated with Kisspeptin-10.

Main Results:

  • CDX2 exhibited the strongest binding to KISS1-DNA, followed by HDAC2, GATA2, NMYC, SP1, and FLI1.
  • Molecular dynamics simulations confirmed stable complexes for SP1, NMYC, and CDX2.
  • Kisspeptin-10 treatment upregulated SP1, NMYC, CDX2, GATA2, and downregulated FLI1 and HDAC2 in TNBC cells.
  • KISS1 selectively modulates TF activity towards anti-metastatic signaling.

Conclusions:

  • KISS1 acts as a selective transcriptional regulator in TNBC metastasis.
  • The findings highlight KISS1's potential as a therapeutic agent against TNBC metastasis.
  • Further research into KISS1-mediated transcriptional regulation could yield novel anti-cancer strategies.
Keywords:
Kisspeptin-10TNBCmolecular dockingmolecular dynamics simulationtranscription factors

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