Neuropilin-1 interacts with integrin beta1 and modulates pancreatic cancer cell growth, survival and invasion

Cancer Biol Ther. 2007 Aug;6(8):1173-80. doi: 10.4161/cbt.6.8.4363. Epub 2007 Apr 29.


Neuropilin-1 (Np-1) is a coreceptor for vascular endothelial growth factor-A (VEGF-A), and both are expressed at high levels in pancreatic ductal adenocarcinomas (PDACs). While VEGF-A has been implicated in tumor angiogenesis, the role of Np-1 in PDAC is less clearly defined. Accordingly, PANC-1 pancreatic cancer cells, which express relatively high levels of Np-1, were transfected with the Np-1 antisense cDNA. By comparison with sham transfected cells, Np-1 antisense expressing clones (Np-1AS) exhibited decreased anchorage independent growth, adhesion and invasiveness, and prolonged doubling times. Np-1AS were also more sensitive to the pro-apoptotic actions of ActD, as evidenced by PARP cleavage, caspase 9 activation and annexin V staining. ActD decreased Bcl-xL and STAT5 levels in the antisense expressing cells, but not in sham-transfected cells, and did not alter STAT3, Bcl-2, phospho-AKT, AKT, Bad, Bax or Bak levels. Immunoprecipitation followed by immunoblotting revealed that Np-1 associated with integrin beta1 and integrin beta1 blockade attenuated adhesion. However, Np-AS expressing clones exhibited enhanced tyrosine phosphorylated focal adhesion kinase. Thus, Np-1 confers a growth and survival advantage to PANC-1 cells, and interacts with integrin beta1 to coordinate signaling events that promote cell adherence and invasiveness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / metabolism
  • Caspase 9 / metabolism
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • DNA, Antisense / pharmacology
  • Dactinomycin / pharmacology
  • Humans
  • Integrin beta1 / metabolism*
  • Neoplasm Invasiveness
  • Neuropilin-1 / antagonists & inhibitors
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • STAT5 Transcription Factor / antagonists & inhibitors
  • STAT5 Transcription Factor / metabolism
  • bcl-X Protein / antagonists & inhibitors
  • bcl-X Protein / metabolism


  • Antibiotics, Antineoplastic
  • Apoptosis Regulatory Proteins
  • DNA, Antisense
  • Integrin beta1
  • STAT5 Transcription Factor
  • bcl-X Protein
  • Neuropilin-1
  • Dactinomycin
  • Poly(ADP-ribose) Polymerases
  • Caspase 9