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

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.

authors
author list (cited authors)
Cho, S. G., Yi, Z., Pang, X., Yi, T., Wang, Y., Luo, J., ... Liu, M.
publication date
2009
published in
keywords
  • 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
altmetric score

3.0

citation count

74