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Research Paper
Neuropilin-1 Interacts with Integrin β1 and Modulates Pancreatic Cancer Cell Growth, Survival and Invasion
Mitsuharu Fukasawa, Akira Matsushita and Murray Korc
volume 6 | issue 8
August 2007Pages: 1173 - 1180
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Neuropilin-1 (Np-1) is a co-receptor 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.
Authors
Mitsuharu Fukasawa
Dartmouth Medical School, Hanover, New Hampshire USA
Akira Matsushita
Dartmouth Medical School, Hanover, New Hampshire USA
Murray Korc
Dartmouth Hitchcock Medical Center; Lebanon, New Hampshire USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.