Sushi repeat-containing protein X-linked 2 promotes angiogenesis through the urokinase-type plasminogen activator receptor dependent integrin αvβ3/focal adhesion kinase pathways

Drug Discov Ther. 2017;11(4):212-217. doi: 10.5582/ddt.2017.01017.

Abstract

Sushi repeat-containing protein X-linked 2 (SRPX2) is a newly identified chondroitin sulfate proteoglycan that is markedly elevated in multiple solid tumors. It is also suggested that SRPX2 is associated with angiogenesis. A conditioned medium of SRPX2 overexpressing colorectal cancer (CRC) cells and SRPX2 recombinant protein was used to evaluate the effect of secretory SRPX2 on the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) and the involved molecular mechanisms. It was revealed that the activity of SRPX2 is dependent on the urokinase-type plasminogen activator receptor and cooperation of the integrin αvβ3 co-receptor. Subsequent studies showed that both PI3K/Akt and Ras/MAPK pathways and phosphorylation of focal adhesion kinase is involved in the intracellular signaling pathway of SRPX2/uPAR. This study suggests that SRPX2 promotes angiogenesis of HUVECs through the cooperation of the uPAR and integrin/FAK pathway.

Keywords: SRPX2; angiogenesis; extracellular matrix; proteoglycan.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / metabolism
  • Culture Media, Conditioned
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • MAP Kinase Signaling System
  • Membrane Proteins
  • Neoplasm Proteins
  • Neovascularization, Pathologic / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • Signal Transduction
  • ras Proteins / metabolism

Substances

  • Culture Media, Conditioned
  • Integrin alphaVbeta3
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Receptors, Urokinase Plasminogen Activator
  • SRPX2 protein, human
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • ras Proteins