title: Involvement of up-regulated Necl-5/Tage4/PVR/CD155 in the loss of contact inhibition in transformed NIH3T3 cells.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minami
authors.forename: Wataru
authors.initials: W
authors.lastname: Ikeda
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kajita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujito
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: 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
chemical_list: D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; C066100:poliovirus receptor; D018631:ras Proteins