Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma

Biochem Biophys Res Commun. 2015 Aug 14;464(1):45-50. doi: 10.1016/j.bbrc.2015.05.092. Epub 2015 May 29.


Spondin 1 (SPON1) is cell adhesion protein that involved in attachment of sensory neuron cells and outgrowth of neurites. Its cellular functions and related mechanisms in cancers, however, remain largely unexplored. In this study, we first identified that SPON1 acts a critical factor in the metastatic progression of osteosarcoma through analysis of a GEO dataset. Then we demonstrated that SPON1 was significantly up-regulated in 72 osteosarcoma specimens compared with benign osteochondroma samples and elevated SPON1 was positively correlated with MMP9 expression. Knockdown of SPON1 expression in two metastatic osteosarcoma cell lines, HKOS and KRIB, dramatically suppressed cell migration and invasion. Treatment with recombinant SPON1 protein in two non-metastatic osteosarcoma cell lines, HOS and U2OS, significantly promoted cell migration and invasion in vitro. Meanwhile, suppression of SPON1 in KHOS cells resulted in decreased pulmonary metastasis in vivo. Mechanistically, we determined that the effects of SPON1 on osteosarcoma cell motility were primarily mediated through Fak and Src dependent pathway. Taken together, our study provides evidence of the contributions of SPON1 and the Fak and Src signaling to the progression of osteosarcoma and suggests that this axis may represent a potential therapeutic target for osteosarcoma.

Keywords: Fak; Osteosarcoma; Spondin 1; Src.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix Proteins / pharmacology
  • Focal Adhesion Kinase 1 / genetics*
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / secondary
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tibia / metabolism
  • Tibia / pathology
  • src-Family Kinases / genetics*
  • src-Family Kinases / metabolism


  • Extracellular Matrix Proteins
  • RNA, Small Interfering
  • SPON1 protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9