A novel peptide blocking cancer cell invasion by structure-based drug design

  • Authors:
    • Yuki Yamada
    • Seiji Kanayama
    • Fuminori Ito
    • Noriyuki Kurita
    • Hiroshi Kobayashi
  • View Affiliations

  • Published online on: July 31, 2017     https://doi.org/10.3892/br.2017.957
  • Pages: 221-225
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Abstract

The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion. The molecular and functional mechanisms of H1 were determined by complementary biochemical and biological methods in the promyeloid U937 cell line as well as ovarian cancer cell lines, including serous carcinoma SKOV3 and clear cell carcinoma TOV21G. The effects of H1 treatment on cancer cell invasion were evaluated in vitro. H1 inhibited cancer cell invasion, without affecting cell viability, accompanied by the suppression of extracellular signal-regulated kinase (ERK)-1 phosphorylation and then matrix metalloproteinase (MMP)-9 expression. H1 failed to block the interaction of uPA‑uPAR protein‑protein interaction in cells, but antagonized the uPA function. H1 failed to disrupt the uPA-uPAR complex, but abolished the invasion of ovarian cancer cells at least through suppression of the ERK-MMP-9 signaling pathway. Further studies are needed to confirm our observations and to describe the underlying molecular mechanism.
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September-2017
Volume 7 Issue 3

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Yamada Y, Kanayama S, Ito F, Kurita N and Kobayashi H: A novel peptide blocking cancer cell invasion by structure-based drug design. Biomed Rep 7: 221-225, 2017
APA
Yamada, Y., Kanayama, S., Ito, F., Kurita, N., & Kobayashi, H. (2017). A novel peptide blocking cancer cell invasion by structure-based drug design. Biomedical Reports, 7, 221-225. https://doi.org/10.3892/br.2017.957
MLA
Yamada, Y., Kanayama, S., Ito, F., Kurita, N., Kobayashi, H."A novel peptide blocking cancer cell invasion by structure-based drug design". Biomedical Reports 7.3 (2017): 221-225.
Chicago
Yamada, Y., Kanayama, S., Ito, F., Kurita, N., Kobayashi, H."A novel peptide blocking cancer cell invasion by structure-based drug design". Biomedical Reports 7, no. 3 (2017): 221-225. https://doi.org/10.3892/br.2017.957