Involvement of up-regulated Necl-5/Tage4/PVR/CD155 in the loss of contact inhibition in transformed NIH3T3 cells.
Normal cells show contact inhibition of cell movement and proliferation, but this is lost following transformation. We found that Necl-5, originally identified as a poliovirus receptor and up-regulated in many cancer cells, enhances growth factor-induced cell movement and proliferation. We showed that when cells contact other cells, Necl-5 interacts in trans with nectin-3 and is removed by endocytosis from the cell surface, resulting in a reduction of cell movement and proliferation. We show here that up-regulation of the gene encoding Necl-5 by the oncogene V12-Ki-Ras causes enhanced cell movement and proliferation. Upon cell-cell contact, de novo synthesis of Necl-5 exceeds the rate of Necl-5 endocytosis, eventually resulting in a net increase in the amount of Necl-5 at the cell surface. In addition, expression of the gene encoding nectin-3 is markedly reduced in transformed cells. Thus, up-regulation of Necl-5 following transformation contributes to the loss of contact inhibition in transformed cells.
Minami
Yukiko
Y
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
Ikeda
Wataru
W
Kajita
Mihoko
M
Fujito
Tsutomu
T
Monden
Morito
M
Takai
Yoshimi
Y
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004705:Endocytosis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D000075983:Nectins; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic / Q000235:genetics*; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; C066100:poliovirus receptor; D018631:ras Proteins