Differential expression of epithelial and mesenchymal proteins in a panel of prostate cancer cell lines.
OBJECTIVE
Epithelial to mesenchymal transition is an important process that results in increased cell migration, invasion and metastasis of many carcinomas. During epithelial to mesenchymal transition epithelial cells down-regulate cell-cell adhesion molecules (ie E-cadherin), up-regulate mesenchymal proteins (ie N-cadherin and cadherin-11), alter polarity, reorganize the cytoskeleton and become isolated. In combination this leads to greater motility. We investigated the role of E-cadherin and the associated catenin-protein complex in regulating epithelial to mesenchymal transition in prostate cancer progression.


METHODS
The relative invasion index of prostate cancer cells was assessed by MTT based in vitro invasion assay. Immunoprecipitation and Western blot were done to determine cadherin-complex formation, and catenin and cadherin protein expression.


RESULTS
Restoration of E-cadherin expression in nonE-cadherin expressing prostate cancer cells decreased invasive potential. However, in vitro invasive potential was tightly regulated by the interaction of cadherin proteins with the catenin complex. E and N-cadherin, cadherin-11, and the catenin proteins α, β, γ and p120 are important for the downstream signaling associated with epithelial to mesenchymal transition in tumor cells.


CONCLUSIONS
Restoration of epithelial specific proteins, such as E-cadherin, in tumor cells can inhibit invasion. However, invasion is a complex process regulated not only by E and N-cadherin but also by catenin-complex proteins. The complex signaling process associated with tumor invasion warrants further investigation since crosstalk between overlapping signaling pathways is involved in regulating prostate cancer invasion, metastasis and progression.
Department of Microbiology and Immunology of the Medical University of South Carolina, Charleston, South Carolina 29403, USA. muraliak@musc.edu
Anuradha Kudur
AK
Murali
James S
JS
Norris
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D051177:Catenins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003599:Cytoskeleton; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D051177:Catenins; C086960:osteoblast cadherin