Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn).
Cadherin cell-cell adhesion proteins play an important role in modulating the behavior of tumor cells. E-cadherin serves as a suppressor of tumor cell invasion, and when tumor cells turn on the expression of a non-epithelial cadherin, they often express less E-cadherin, enhancing the tumorigenic phenotype of the cells. Here, we show that when A431 cells are forced to express R-cadherin, they dramatically downregulate the expression of endogenous E- and P-cadherin. In addition, we show that this downregulation is owing to increased turnover of the endogenous cadherins via clathrin-dependent endocytosis. p120(ctn) binds to the juxtamembrane domain of classical cadherins and has been proposed to regulate cadherin adhesive activity. One way p120(ctn) may accomplish this is to serve as a rheostat to regulate the levels of cadherin. Here, we show that the degradation of E-cadherin in response to expression of R-cadherin is owing to competition for p120(ctn).
Maeda
M
M
Department of Oral Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Johnson
E
E
Mandal
S H
SH
Lawson
K R
KR
Keim
S A
SA
Svoboda
R A
RA
Caplan
S
S
Wahl
J K
JK
Wheelock
M J
MJ
Johnson
K R
KR
D001667:Binding, Competitive; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012878:Skin Neoplasms / Q000378:metabolism*; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; C083970:R-cadherin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human