Neuropilin-1 interacts with integrin β1 and modulates pancreatic cancer cell growth, survival and invasion

Mitsuharu Fukasawa, Akira Matsushita, Murray Korc

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

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 β1, and integrin β1 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 β1 to coordinate signaling events that promote cell adherence and invasiveness.

Original languageEnglish (US)
Pages (from-to)1184-1191
Number of pages8
JournalCancer Biology and Therapy
Volume6
Issue number8
StatePublished - Aug 2007

Keywords

  • Adhesion
  • Antisense
  • Apoptosis
  • Bcl-xL
  • Integrin
  • Neuropilin-1
  • Pancreatic cancer
  • STAT5

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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