Suppression of cell growth by ectopic expression of N-cadherin.
We found that ectopic expression of N-cadherin in 3Y1 caused tight association of cells and, thereby, substantially suppressed cell growth. N-cadherin expression inhibited neither tyrosine phosphorylation of cellular proteins, GTP uptake onto Ras, nor activation of MAP kinase, suggesting that it does not directly interfere the Ras-MAP kinase pathway. However, co-expression of N-cadherin with dominant negative Ras, S17N Ras, showed synergestic growth inhibitory effect, suggesting that N-cadherin signaling antagonizes the Ras-MAP kinase signaling. In addition, we found that N-cadherin yielded cell-cycle arrest at G0/G1 phase. These results strongly suggest that N-cadherin cell adhesion machinery works as a negative controller of cell cycle in 3Y1 and this growth suppressive function of cadherin is distinct from the epithelial morphogenetic function.
Wang
X
X
Department of Molecular Pathogenesis, Nagoya University School of Medicine, 65-Tsurumai-cho, Showa-Ku, Nagoya 466, Japan.
Thant
A A
AA
Machida
K
K
Hiraiwa
Y
Y
Iwata
H
H
Matsuda
S
S
Hamaguchi
M
M
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D016193:G1 Phase; D011905:Genes, ras; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle; D014162:Transfection; D018631:ras Proteins / Q000096:biosynthesis / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D011994:Recombinant Proteins; D003907:Dexamethasone; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins