Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library
| Autor: | Yaoling Xiong, Fei Xiao, Zhijian Su, Qihao Zhang, Cuizan Cai, Qi Xiang, Qing Zheng, Mengyang Lian, Guofeng Lou, Yadong Huang, Xiaoyong Dai |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Phage display
MAP Kinase Signaling System Biophysics Antineoplastic Agents Breast Neoplasms Biopanning Biology Biochemistry Cyclin D1 Peptide Library Cell Line Tumor Proliferating Cell Nuclear Antigen Humans Amino Acid Sequence Breast Receptor Molecular Biology Adaptor Proteins Signal Transducing Cell Proliferation Cell growth Fibroblast growth factor receptor 1 Cell Cycle RNA-Binding Proteins Cell Biology Cell cycle Molecular biology Enzyme Activation Fibroblast growth factor receptor Fibroblast Growth Factor 1 Female Peptides Proto-Oncogene Proteins c-akt |
| Zdroj: | Biochemical and Biophysical Research Communications. 445:795-801 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.02.022 |
| Popis: | It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182-188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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