M1-NP1 interfering-peptide inhibits cancer cell proliferation and migration by targeting the transcription factor

Chaozhu Pei1, Ziwu Xu1, Min Ouyang1

  • 1State Key Laboratory of Chemo and Biosensing, College of Biology, Hunan Research Center of the Basic Discipline for Cell Signaling, Hunan Engineering Research Center for Anticancer Targeted Protein Pharmaceuticals, Hunan University, Changsha, 410082, China.

Insights

A novel peptide, M1-NP1, effectively targets the FOXM1 transcription factor to inhibit cancer cell proliferation and migration. This peptide shows promise as a safe and effective cancer therapeutic agent with minimal side effects.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Discovery

Background:

  • The transcription factor forkhead (FOX) box M1 (FOXM1) is overexpressed in multiple cancers.
  • FOXM1 is a promising target for novel cancer drug development.

Purpose of the Study:

  • To identify and characterize a novel FOXM1-targeting peptide for cancer therapy.
  • To investigate the mechanism of action and therapeutic potential of the identified peptide.

Main Methods:

  • Yeast-two-hybrid (Y2H) screening was employed to discover FOXM1-interacting peptides.
  • In vitro assays assessed the peptide's effects on cancer cell cycle and migration.
  • In vivo studies in wild-type mice evaluated the peptide's efficacy and safety profile.

Main Results:

  • A novel peptide, M1-NP1, was identified that binds to FOXM1's C-terminal region.
  • M1-NP1 inhibits FOXM1 transcriptional activity by disrupting interactions with PLK1 and CBP.
  • M1-NP1 treatment reduced cancer cell proliferation and migration, downregulated cell cycle genes, and upregulated cell adhesion genes.
  • M1-NP1 demonstrated anti-cancer effects in vivo without significant toxicity, showing good stability and distribution.

Conclusions:

  • M1-NP1 is a potent inhibitor of FOXM1 transcriptional activity.
  • M1-NP1 exhibits promising anti-cancer efficacy and a favorable safety profile, making it a potential candidate for cancer therapy.

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