The CD155/poliovirus receptor enhances the proliferation of ras-mutated cells.
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 G0/G1 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 CD155DeltaCP, 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 CD155DeltaCP 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.
Kono
Tokuyuki
T
Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Imai
Yasuo
Y
Yasuda
Shin-ichi
S
Ohmori
Kyoko
K
Fukui
Hirokazu
H
Ichikawa
Kazuhito
K
Tomita
Shigeki
S
Imura
Johji
J
Kuroda
Yoshikazu
Y
Ueda
Yoshihiko
Y
Fujimori
Takahiro
T
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018631:ras Proteins