Kisspeptin-10, a KISS1-derived decapeptide, inhibits tumor angiogenesis by suppressing Sp1-mediated VEGF expression and FAK/Rho GTPase activation | Academic Article individual record

Kisspeptin-10 (Kp-10), a decapeptide derived from the primary translation product of KISS1 gene, has been reported previously to be a key hormone for puberty and an inhibitor for tumor metastasis via the activation of G protein-coupled receptor 54. However, whether Kp-10 inhibits angiogenesis, which is critical for tumor growth and metastasis and other human diseases, is still unknown. Here we show that Kp-10 significantly inhibits human umbilical vein endothelial cell (HUVEC) migration, invasion, and tube formation, key processes in angiogenesis. Using chicken chorioallantoic membrane assay and vascular endothelial growth factor (VEGF)-induced mouse corneal micropocket assay, we show that Kp-10 inhibits angiogenesis in vivo. Furthermore, Kp-10 inhibits tumor growth in severe combined immunodeficient mice xenografted with human prostate cancer cells (PC-3) through inhibiting tumor angiogenesis, whereas Kp-10 has little effect on the proliferation of HUVECs and human prostate cancer cells. In deciphering the underlying molecular mechanisms, we show that Kp-10 suppresses VEGF expression by inhibiting the binding of specificity protein 1 to VEGF promoter and by blocking the activation of c-Src/focal adhesion kinase and Rac/Cdc42 signaling pathways in HUVECs, leading to the inhibition of tumor angiogenesis. ©2009 American Association for Cancer Research.

author list (cited authors)
Cho, S. G., Yi, Z., Pang, X., Yi, T., Wang, Y., Luo, J., ... Liu, M.
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  • Neovascularization, Physiologic
  • Mice
  • Tumor Suppressor Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • Humans
  • Xenograft Model Antitumor Assays
  • Chick Embryo
  • Wound Healing
  • Chorioallantoic Membrane
  • Neovascularization, Pathologic
  • Neoplasms, Experimental
  • Focal Adhesion Kinase 1
  • Endothelial Cells
  • Dose-Response Relationship, Drug
  • Vascular Endothelial Growth Factor A
  • Oligopeptides
  • Cell Movement
  • Cell Adhesion
  • Cell Line, Tumor
  • Angiogenesis Inhibitors
  • Kisspeptins
  • Animals
  • Cell Proliferation
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