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Published on: October 30, 2013
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.
Abstract:
Multiple cancers overexpress forkhead (FOX) box M1 (FOXM1), a transcription factor (TF) that holds great promise for developing cancer drugs. Herein, through yeast-two-hybrid (Y2H) screening, we obtained a novel FOXM1-targeting peptide M1-NP1, which significantly inhibited the cell cycle and migration of cancer cells. Mechanistically, M1-NP1 bound to the C-terminal region of FOXM1 and disrupted its interactions with the cell cycle-related kinase polo-like kinase 1 (PLK1) and the transcriptional co-activator cyclic adenosine monophosphate (AMP) response element-binding protein (CREB) binding protein (CBP), thus inhibiting FOXM1 transcriptional activities. Additionally, M1-NP1 affected FOXM1 distribution in cells, preventing FOXM1 from infiltrating the nucleus to exert its effects. Furthermore, M1-NP1 treatment in cancer cells downregulated the gene sets of cell cycle phase transition and upregulated the gene sets of cell adhesion. Moreover, M1-NP1's anti-cancer effects were confirmed in wild-type (WT) mice, without any notable toxic or side effects. In addition to its good safety indications, such as the low levels of immunogenicity and hemolysis, M1-NP1 also exhibited a favorable profile regarding stability and distribution in mice. Overall, M1-NP1 targets FOXM1 for cancer therapy.
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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