Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3.
Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor-induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell-cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell-cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell-cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation.
Fujito
Tsutomu
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
Ikeda
Wataru
W
Kakunaga
Shigeki
S
Minami
Yukiko
Y
Kajita
Mihoko
M
Sakamoto
Yasuhisa
Y
Monden
Morito
M
Takai
Yoshimi
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002966:Clathrin / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D051379:Mice; D041681:NIH 3T3 Cells; D000075983:Nectins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D002966:Clathrin; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C476587:Taa1 protein, mouse