The CD155/poliovirus receptor enhances the proliferation of ras-mutated cells

✍ Scribed by Tokuyuki Kono; Yasuo Imai; Shin-ichi Yasuda; Kyoko Ohmori; Hirokazu Fukui; Kazuhito Ichikawa; Shigeki Tomita; Johji Imura; Yoshikazu Kuroda; Yoshihiko Ueda; Takahiro Fujimori

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 461 KB
• Volume: 122
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23080

✦ Synopsis

Abstract

Stimulation of the CD155/poliovirus receptor, which localizes in the cell–matrix and at cell–cell junctions, inhibits cell adhesion and enhances cell migration. Necl‐5, a mouse homolog of CD155, is implicated in the formation of adherence junctions. Recently, Necl‐5 has also been found to enhance cell proliferation via the stimulation of serum and platelet‐derived growth factor through the Ras‐Raf‐MEK‐ERK signaling pathway. In our present study, we find that CD155 significantly enhances the serum‐induced cell proliferation of NIH3T3 cells which have been transformed by an oncogenic Ras (V12Ras‐NIH3T3), but not the parental cells. CD155 expression in V12Ras‐NIH3T3 cells is also found to upregulate cyclin D2, downregulate p27^Kip1^ and shorten the G~0~/G~1~ phase of the cell cycle. An inhibitor of focal adhesion kinase does not reduce this CD155‐mediated enhancement of V12Ras‐NIH3T3 cell proliferation. The expression of CD155ΔCP, which lacks the cytoplasmic region including the immunoreceptor tyrosine‐based inhibitory motif (ITIM), has a reduced ability to enhance the serum responsiveness of V12Ras‐NIH3T3 cells, suggesting that the ITIM might be required for this effect of CD155. In addition, the overexpression of exogenous CD155 enhances the serum responsiveness of HT1080 cells, which harbor a mutant N‐ras gene. On the other hand, siRNA‐induced knockdown of endogenous CD155 and/or CD155ΔCP expression significantly repress the serum responsiveness of DLD‐1 cells, which express endogenous CD155 and harbor a mutant K‐ras gene, suggesting that this mutant may function in a dominant negative manner. Taken together, our present data suggest that CD155, at least in part, enhances the proliferation of ras‐mutated cells. © 2007 Wiley‐Liss, Inc.