p120ctn and P-cadherin but not E-cadherin regulate cell motility and invasion of DU145 prostate cancer cells.
BACKGROUND
Adherens junctions consist of transmembrane cadherins, which interact intracellularly with p120ctn, beta-catenin and alpha-catenin. p120ctn is known to regulate cell-cell adhesion by increasing cadherin stability, but the effects of other adherens junction components on cell-cell adhesion have not been compared with that of p120ctn.


RESULTS
We show that depletion of p120ctn by small interfering RNA (siRNA) in DU145 prostate cancer and MCF10A breast epithelial cells reduces the expression levels of the adherens junction proteins, E-cadherin, P-cadherin, beta-catenin and alpha-catenin, and induces loss of cell-cell adhesion. p120ctn-depleted cells also have increased migration speed and invasion, which correlates with increased Rap1 but not Rac1 or RhoA activity. Downregulation of P-cadherin, beta-catenin and alpha-catenin but not E-cadherin induces a loss of cell-cell adhesion, increased migration and enhanced invasion similar to p120ctn depletion. However, only p120ctn depletion leads to a decrease in the levels of other adherens junction proteins.


CONCLUSIONS
Our data indicate that P-cadherin but not E-cadherin is important for maintaining adherens junctions in DU145 and MCF10A cells, and that depletion of any of the cadherin-associated proteins, p120ctn, beta-catenin or alpha-catenin, is sufficient to disrupt adherens junctions in DU145 cells and increase migration and cancer cell invasion.
Kümper
Sandra
S
Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom.
Ridley
Anne J
AJ
D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D008297:Male; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human